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Page 1 of 177
FORM-1
FOR
PROPOSED PHARMA & PHARMA INTERMEDIATES
MANUFACTURING UNIT
OF
M/s. KESHAV INTERCHEM
PLOT NO. 905/11/8, GIDC ESTATE,
PANOLI-394 116, TALUKA: ANKLESHWAR,
DISTRICT: BHARUCH, GUJARAT
Prepared by:
Aqua-Air Environmental Engineers Pvt. Ltd.
(Pollution Control Consultants & Engineers)
Reg. Office: 403, Centre Point, Nr. Kadiwala School, Ring Road,
Surat – 395 002, Gujarat, India Fax: +91 261 2707273 / 3987273
Tel: + 91 261 3048586 / 2460854 / 2461241
E-mail: aquaair_surat@hotmail.com Visit us at: www.aqua-air.co.in
Page 2 of 177
APPENDIX I
(See paragraph - 6)
FORM 1
Sr.
No.
Item Details
1. Name of the project/s M/s. Keshav Interchem
2. S. No. in the schedule 5 (f)
3. Proposed capacity/area/length/tonnage
to be handled/command area/lease
area/number of wells to be drilled
Proposed Capacity = 15 MT/Month
Total Plot Area = 2,767.18 m2
4. New/Expansion/Modernization New
5. Existing Capacity/Area etc. For detail Please refer Annexure – I
6. Category of Project i.e. ‘A’ or ‘B’ ‘A’
7. Does it attract the general condition? If
yes, please specify.
Yes. Located within 5 km of critically
polluted area (Ankleshwar).
8. Does it attract the specific condition? If
yes, please specify.
No
Location
Plot/Survey/Khasra No. Plot No. 905/11/8
Village GIDC estate, Panoli
Tehsil Ankleshwar
District Bharuch
9.
State Gujarat
10. Nearest railway station/airport along
with distance in kms.
Railway Station: Ankleshwar (4.5 km)
Airport: Surat (60 km)
11. Nearest Town, city, District
Headquarters along with distance in
kms.
Panoli Village (3 km)
Bharuch (15.5 km)
12. Village Panchayats, Zilla Parishad,
Municipal Corporation, local body
(complete postal address with
telephone nos. to be given)
Notified Area Authority, Panoli
13. Name of the applicant M/s. Keshav Interchem
14. Registered Address Plot No. 905/11/8, GIDC estate,
Panoli-394116, Taluka: Ankleshwar,
District: Bharuch, Gujarat
Address for correspondence:
Name Ms. Rutu Mahendrabhai Patel
Designation (Owner/Partner/CEO) Proprietor
15.
Address M/s. Keshav Interchem
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A-1/32, Nirman complex, R. C.
Technical Road, Chankyapuri,
Ghatlodia, Ahmadabad- 386001 (Guj.)
Pin Code 386001
E-mail keshavinterchem@gmail.com
Telephone No. --
Fax No. --
Mobile No. +919429437733, +917203055448
16. Details of Alternative Sites examined, if
any.
Location of these sites should be shown
on a topo sheet.
NA
17. Interlinked Projects No
18. Whether separate application of
interlinked project has been submitted?
No
19. If yes, date of submission No
20. If no, reason No
21. Whether the proposal involves
approval/clearance under: if yes, details
of the same and their status to be
given.
(a) The Forest (Conservation) Act, 1980?
(b) The Wildlife (Protection) Act, 1972?
(c) The C.R.Z. Notification, 1991?
No
22. Whether there is any Government
Order/Policy relevant/relating to the
site?
No
23. Forest land involved (hectares) No
24. Whether there is any litigation pending
against the project and/or land in which
the project is propose to be set up?
(a) Name of the Court
(b) Case No.
(c) Orders/directions of the Court, if any
and its relevance with the proposed
project.
No
• Capacity corresponding to sectoral activity (such as production capacity for
manufacturing, mining lease area and production capacity for mineral production,
area for mineral exploration, length for linear transport infrastructure, generation
capacity for power generation etc.,)
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(II) Activity
1. Construction, operation or decommissioning of the Project involving actions, which will cause physical changes in the locality (topography, land use, changes in water bodies, etc.)
Sr.
No.
Information/Checklist confirmation Yes
/No
Details thereof with approximate
quantities frates, wherever
possible) with source of information
data
1.1 Permanent or temporary change in land use, land cover or topography including increase intensity of land use (with respect to local land use plan)
No Proposed project activity is within the Panoli GIDC Industrial Estate.
1.2 Clearance of existing land,
vegetation and Buildings?
Yes Minor site clearance activities shall be carried out to clear shrubs and weed.
1.3 Creation of new land uses?
No The project site is located on level ground, which does not require any major land filling for area grading work.
1.4 Pre-construction investigations e.g.
bore Houses, soil testing?
No Proposed site is located within earmarked industrial estate developed by GIDC.
1.5 Construction works? Yes Please refer Annexure – I.
1.6 Demolition works? No There will be not any demolition work at the site.
1.7 Temporary sites used for
construction works or housing of
construction workers?
No Proposed site is located within notified industrial estate developed by GIDC and all required manpower will be employed from nearby area.
1.8 Above ground buildings, structures
or earthworks including linear
structures, cut and fill or excavations
Yes Please refer Annexure – I.
1.9 Underground works mining or
tunneling?
No Not Required
1.10 Reclamation works? No Not Required
1.11 Dredging? No Not Required
1.12 Off shore structures? No Not Required
1.13 Production and manufacturing
processes?
Yes Please refer Annexure – III.
1.14 Facilities for storage of goods or
materials?
Yes Areas for storage of raw materials and finished products will be developed.
1.15 Facilities for treatment or disposal of
solid waste or liquid effluents?
Yes For Facilities for treatment & disposal of liquid effluents please refer Annexure – V. For Hazardous waste details please refer Annexure – VII.
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1.16 Facilities for long term housing of
operational workers?
No Not Concerned
1.17 New road, rail or sea traffic during
Construction or operation?
No There will be very minor traffic increase due to proposed project and will not cause any change in locality.
1.18 New road, rail, air waterborne or
other transport infrastructure
including new or altered routes and
stations, ports, airports etc?
No Proposed site is located within notified industrial estate having very well developed infrastructure facilities. Therefore, there will not be any need of new transportation route/station.
1.19 Closure or diversion of existing
transport routes or infrastructure
leading to changes in Traffic
movements?
No Not Applicable
1.20
New or diverted transmission lines or
Pipelines?
No Proposed site is situated in notified industrial estate having very well developed transmission lines or pipelines for resources and effluent handling. Therefore, there will not be any need of new or diverted transmission lines or pipelines.
1.21 Impoundment, damming, culverting,
realignment or other changes to the
hydrology of watercourses or
aquifers?
No Water required will be met through GIDC Water Supply.
1.22 Stream crossings? No Not Required
1.23 Abstraction or transfers of water
form ground or surface waters?
Yes Water requirement will be met through Panoli GIDC water supply.
1.24 Changes in water bodies or the land
surface affecting drainage or run-off?
No Not Concerned
1.25 Transport of personnel or materials
for construction, operation or
decommissioning?
Yes Transportation of personnel or raw material and products will be primarily by road only.
1.26 Long-term dismantling or
decommissioning or restoration
works?
No Not Required
1.27 Ongoing activity during
decommissioning which could have
an impact on the environment?
No Not Concerned
1.28 Influx of people to an area either
temporarily or permanently?
Yes Direct/Indirect employment shall be provided for proposed operation.
1.29 Introduction of alien species? No Not Concerned
1.30 Loss of native species or genetic
diversity?
No Not Concerned
1.31 Any other actions? No Not Concerned
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2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or energy, especially any resources which are non-renewable or in short supply):
Sr.
No.
Information/checklist confirmation Yes/
No
Details thereof (with approximate
quantities /rates, wherever
possible) with source of information
data
2.1 Land especially undeveloped or
agricultural land (ha)
No Proposed project activity will be
within GIDC Industrial Area, Panoli,
District: Bharuch, Gujarat.
2.2 Water (expected source & competing
users) unit: KLD
Yes Water Source: Panoli GIDC Water
Supply. For details please refer
Annexure – IV.
2.3 Minerals (MT) No Not Required
2.4 Construction material – stone,
aggregates, and / soil
(expected source – MT)
Yes Construction materials, like steel,
cement, crushed stones, sand,
rubble, etc. required for the project
shall be procured from the local
market of the region.
2.5 Forests and timber (source – MT) No Not Required
2.6 Energy including electricity and fuels
(source, competing users) Unit: fuel
(MT), energy (MW)
Yes Power required will be 400 KVA
Source: DGVCL
Note: DG Set 100 KVA will be kept
for emergency power back up.
Fuel Requirement:
Natural Gas = 500 SM3/Day
Diesel = 50 Liter/Day
2.7 Any other natural resources
(use appropriate standard units)
No Not Required
3. Use, storage, transport, handling or production of substances or materials, which could
be harmful to human health or the environment or raise concerns about actual or
perceived risks to human health.
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
3.1 Use of substances or materials, which
are hazardous (as per MSIHC rules) to
human health or the environment
(flora, fauna, and water supplies)
Yes Please refer Annexure – VIII.
3.2 Changes in occurrence of disease or
affect disease vectors (e.g. insect or
water borne diseases)
No Not Required
3.3 Affect the welfare of people e.g. by
changing living conditions?
No The project will bring direct / indirect
employment opportunity, which will
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enhance the socio-economic status
of the area.
3.4 Vulnerable groups of people who
could be affected by the project e.g.
hospital patients, children, the
elderly etc.
No Proposed site is located within
notified industrial estate developed
by GIDC.
3.5 Any other causes No Not Required
4. Production of solid wastes during construction or operation or decommissioning
(MT/month)
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
4.1 Spoil, overburden or mine wastes No Not Applicable
4.2 Municipal waste (domestic and or
commercial wastes)
Yes Through Septik Tank / Soak Pit
4.3 Hazardous wastes (as per Hazardous
Waste Management Rules)
Yes Please refer Annexure – VII.
4.4 Other industrial process wastes Yes Please refer Annexure – VII.
4.5 Surplus product No
There will not be any surplus
product.
4.6 Sewage sludge or other sludge from
effluent treatment Yes
Please refer Annexure – VII.
4.7 Construction or demolition wastes
Yes
Construction waste shall be utilized
for leveling, land filling in the
premises.
4.8 Redundant machinery or equipment No
All machinery / equipment will be
installed as per requirement.
4.9 Contaminated soils or other
materials No Not Concerned
4.10 Agricultural wastes No Not Concerned
4.11 Other solid wastes Yes
Please refer Annexure – VII.
5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr)
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
5.1 Emissions from combustion of fossil
fuels from stationary or mobile
sources
Yes Please refer Annexure – VI.
5.2 Emissions from production processes Yes Please refer Annexure – VI.
5.3 Emissions from materials handling
storage or transport
Yes Solid raw materials shall be charged
through close pipeline into reactors
Page 8 of 177
and the dust collection hopper shall
be connected to a bag filter and ID
fan.
5.4 Emissions from construction
activities including plant and
equipment
Yes During construction work, only dust
contamination will be there & water
sprinklers shall be utilized whenever
necessary.
5.5 Dust or odours from handling of
materials including construction
materials, sewage and waste
No Dust from drying will be collected in
to dust collector through cyclone
separator & recovered powder will
be recycled back to process. Air
Handling Unit will be provided where
ever applicable.
5.6 Emissions from incineration of waste
No There will not be incineration of
waste.
5.7 Emissions from burning of waste in
open air e.g. slash materials,
construction debris)
No
No open burning will be carried out
within premises.
5.8 Emissions from any other sources Yes Please refer Annexure – VI.
6. Generation of Noise and Vibration, and Emissions of Light and Heat:
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data with
source of information data
6.1 From operation of equipment e.g.
engines, ventilation plant, crushers
Yes The Noise level will be within the
prescribed limit. At noisy areas
adequate preventive & control
measures will be taken. No
significant noise, vibration or
emission of light & heat from the
unit.
6.2 From industrial or similar processes Yes All machinery / equipment shall be
well maintained, shall be proper
foundation with anti vibrating pads
wherever applicable and noise levels
within permissible limits.
Acoustic enclosures shall be provided 6.3 From construction or demolition No Minor noise will be generated during
construction work.
6.4 From blasting or piling No No blasting or pilling will be carried
out at project site.
6.5 From construction or operational
traffic
No Not Concerned
6.6 From lighting or cooling systems No Not Concerned
Page 9 of 177
6.7 From any other sources No Not Concerned 7. Risks of contamination of land or water from releases of pollutants into the ground or
into sewers, surface waters, groundwater, coastal waters or the sea:
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
7.1 From handling, storage, use or
spillage of hazardous materials
Yes Please refer Annexure – VIII.
7.2 From discharge of sewage or other
effluents to water or the land
(expected mode and place of
discharge)
Yes Sewage shall be treated in Septic
Tank / Soak Pit.
For details please refer Annexure – V.
7.3 By deposition of pollutants emitted
to air into the and or into water
No Not Concerned
7.4 From any other sources No Not Concerned
7.5 Is there a risk of long term build up of
pollutants in the environment from
these sources?
No Not Concerned
8. Risk of accidents during construction or operation of the Project, which could affect
human health or the environment
Sr.
No.
Information/Checklist confirmation Yes/
No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
8.1 From explosions, spillages, fires etc
from storage, handling, use or
production of hazardous substances
Yes Please refer Annexure – VIII.
8.2 From any other causes No Not Concerned
8.3 Could the project be affected by
natural disasters causing
environmental damage (e.g. floods,
earthquakes, landslides, cloudburst
etc)?
No Not Concerned
9. Factors which should be considered (such as consequential development) which could lead to environmental effects or the potential for cumulative impacts with other existing or planned activities in the locality
Sr. No.
Information/Checklist confirmation
Yes/ No
Details there of (with approximate
quantities/rates, wherever possible)
with source of information data
9.1 Lead to development of supporting. utilities, ancillary development or development stimulated by the project which could have impact on
Yes Please refer Annexure – IX.
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the environment e.g. • Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.)
• housing development • extractive industry • supply industry • other
9.2 Lead to after-use of the site, which
could have an impact on the
environment
No Not Concerned
9.3 Set a precedent for later
developments
No Not Concerned
9.4 Have cumulative effects due to
proximity to other existing or
planned projects with similar effects
No Not Concerned
(III) Environmental Sensitivity
Sr.
No.
Areas Name/
Identity
Aerial distance (within 5 km)
Proposed project location boundary
1 Areas protected under international
conventions, national or local
legislation for their ecological,
landscape, cultural or other related
value
No No protected area within 5 km from
the proposed project site.
2 Areas which important for are or
sensitive Ecol logical reasons -
Wetlands, watercourses or other
water bodies, coastal zone,
biospheres, mountains, forests
Yes River Narmada = 11 km
3 Area used by protected, important or
sensitive Species of flora or fauna for
breeding, nesting, foraging, resting,
over wintering, migration
No Not Concerned
4 Inland, coastal, marine or
underground waters
No Not Concerned
5 State, National boundaries No No state or national boundary falls
within 5 km aerial distance from the
project site.
6 Routes or facilities used by the public
for access to recreation or other
tourist, pilgrim areas.
Yes Public transportation
7 Defense installations Yes Ankleshwar
8 Densely populated or built-up area Yes Panoli village 3 km and Ankleshwar
City around 4.5 km from the
proposed project site.
Page 11 of 177
9 Area occupied by sensitive man-made
land uses Hospitals, schools, places of
worship, community facilities)
No Not Applicable
10 Areas containing important, high
quality or scarce resources (ground
water resources, surface resources,
forestry, agriculture, fisheries,
tourism, minerals)
No Not Concerned
11 Areas already subjected to pollution
environmental damage. (those where
existing legal environmental standards
are exceeded)
Yes Ankleshwar
12 Areas susceptible to natural hazard
which could cause the project to
present environmental problems
(earthquakes, subsidence, landslides,
flooding erosion, or extreme or
adverse climatic conditions)
No Not Applicable
IV). Proposed Terms of Reference for EIA studies: Please refer Annexure - X
I hereby given undertaking that, the data and information given in the application and
enclosures are true to the best of my knowledge and belief and I am aware that if any part of
the data and information submitted is found to be false or misleading at any stage the project
will be rejected and clearance give, if any to the project will be revoked at our risk and cost.
Date: August 6, 2017
Place: GIDC, Panoli
NOTE:
1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall
submit with the application a C.R.Z. map duly demarcated by one of the authorized agencies,
showing the project activities, w.r.t. C.R.Z. (at the stage of TOR) and the recommendations of
the State Coastal Zone Management Authority (at the stage of EC). Simultaneous action shall
also be taken to obtain the requisite clearance under the provisions of the C.R.Z. Notification,
1991 for the activities to be located in the CRZ.
2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere
Reserves, Migratory Corridors of Wild Animals, the project proponent shall submit the map
duly authenticated by Chief Wildlife Warden showing these features vis-à-vis the project
location and the recommendations or comments of the Chief Wildlife Warden thereon (at the
stage of EC).
Page 12 of 177
3. All correspondence with the Ministry of Environment & Forests including submission of
application for TOR/Environmental Clearance, subsequent clarifications, as may be required
from time to time, participation in the EAC Meeting on behalf of the project proponent shall
be made by the authorized signatory only. The authorized signatory should also submit a
document in support of his claim of being an authorized signatory for the specific project.
Page 13 of 177
LIST OF ANNEXURES
SR. NO. NAME OF ANNEXURE
I Layout Map of the Plant
II List of Products and Raw materials along with their Production Capacity
III Brief Manufacturing Process Description
IV Details of water consumption & waste water generation
V Details of Effluent Treatment Scheme
VI Details of Air Pollution Control System
VII Details of Hazardous Waste Generation and Disposal
VIII Details of Hazardous Chemicals Storage & Handling
IX Socio-economic Impacts
X Proposed Terms of Reference
XI Copy of Plot Allotment Letter
XII Copy of GIDC Water Supply Certificate
XIII Membership Certificate of CETP (M/s. PETL)
XIV Membership Certificate of Common Solid Waste Disposal Facility & Common
Incineration Facility (M/s. BEIL)
XV Toposheet
Page 14 of 177
ANNEXURE - I
___________________________________________________________________________
LAYOUT OF MAP OF THE PLANT
Page 15 of 177
ANNEXURE - II
____________________________________________________________________________
LIST OF PRODUCTS ALONG WITH THEIR PRODUCTION CAPACITY
SR.
NO. PRODUCT NAME CAS NO.
QUANTITY
MT / MONTH
Group – I
1 Phenylephrine hcl AND/OR 61-76-7
2 Ofloxacin AND/OR 82419-36-1
3 Olanzapine AND/OR 132539-06-1
4 Hydrochlorothiazide AND/OR 58-93-5
5 Oxcarbazepine AND/OR 28721-07-5
6 10-Methoxy-5H-dibenz[b,f]azepine-5-
carbonylchloride, 10-Methoxyiminostilbene-5-
carbonylchloride AND/OR
28721-08-6
7 Diclofenac sodium AND/OR 15307-79-6
8 2,6 – dichloro diphenyl amine (dcdpa) AND/OR 15307-93-4
9 N-chloroacetyl-n-phenyl-2,6-dichloro aniline
(cpdca) AND/OR
15308-01-7
10 Indolenone [ (n-1) of dicofenac ] AND/OR 15362-40-0
11 2-Hydroxymethyl-3-methyl-4-(3-methoxy
propanoxyl)pyridine HCL AND/OR
153259-31-5
12 1,2-benisoxazole-3-acetica acid AND/OR 37924-67-7
13 Cis-tosylate AND/OR 134071-44-6
14 Atorvastatin calcium AND/OR 134523-03-8
15 tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-
isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-
yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate
AND/OR
65564-05-8
16 Nebivolol Hydrochloride AND/OR 152520-56-4
17 Pantaprazol Sodium AND/OR 138786-67-1
18 5-(Difluoromethoxy)-2- {[( 3,4Dimethoxypyridin - 2-
yl) methyl]thio}-1H-benzimidazolee AND/OR
102625-64-9
19 N-((4-Chloromethyl)-2-Thiozolyl)Guanidine
Hydrochloride AND/OR
84545-70-0
20 Methyl 3-amino-2 butenoate AND/OR 14205-39-1
21 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl)
Acetophenone (Dfta) AND/OR
86404-63-9
22 cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-
ylmethyl)-1,3-dioxolan-4-ylmethyl methane
67914-86-7
7.0
Page 16 of 177
SR.
NO. PRODUCT NAME CAS NO.
QUANTITY
MT / MONTH
sulphonate AND/OR
23 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine
AND/OR
74852-61-2
24 2-[[4-(2-Methoxyethyl)phenoxy]methyl-oxirane
AND/OR
56718-70-8
25 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy)
benzanilide AND/OR
136450-06-1
Group – II
26 Prasugrel Hydrochloride AND/OR 389574-19-0
27 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl] -
5,6,7,7a-tetrahydrothieno[3,2-c]pyridin-2(4H)-one
AND/OR
150322-38-6
28 Dabigatran AND/OR 211915-06-9
29 Femotidine AND/OR 76824-35-6
30 N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L valine
methyl ester AND/OR
137863-89-9
31 Amlodipin besylate AND/OR 111470-99-6
32 Amlodipine base AND/OR 88150-42-9
33 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1-
piperazinyl)phenyl]-2-(1-methylpropyl)-3h-1,2,4-
triazole-3-one AND/OR
106461-41-0
34 Metoprolol tartrate AND/OR 56392-17-7
35 1-(Isopropylamino)-3-[4-(2-methoxyethyl)
phenoxy]-2-propanol AND/OR
37350-58-6
36 Metoprolol succinate AND/OR 98418-47-4
37 Ketoconazole AND/OR 65277-42-1
38 Phthaloyl amlodipine AND/OR 88150-62-3
39 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-
piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-
triazol-3-one AND/OR
252964-68-4
5.0
Group – III
40 Montelukast sodium AND/OR 151767-02-1
41 Valsartan AND/OR 137862-53-4
42 Venlafaxine Hydrochloride AND/OR 99300-78-4
43 Levocetirizine Dihydrochloride AND/OR 130018-77-8
44 Pregabalin AND/OR 148553-50-8
45 Veratric Acid AND/OR 93-07-2
46 Fluconazole AND/OR 86386-73-4
47 Itraconazole AND/OR 84625-61-6
3.0
Page 17 of 177
SR.
NO. PRODUCT NAME CAS NO.
QUANTITY
MT / MONTH
48 Cetirizine Dihydrochloride AND/OR 83881-51-0
49 Rabeprazole sodium AND/OR 117976-90-6
50 Pranlukast AND/OR 103177-37-3
51 Zonisamide AND/OR 68291-97-4
52 Telmisartan AND/OR 144701-48-4
53 Rosuvastatine calcium AND/OR 147098-20-2
54 Posaconazole AND/OR 1712228-49-2
55 Ursodiol AND/OR 128-13-2
TOTAL QUANTITY PRODUCTION PER MONTH 15
Page 18 of 177
LIST OF RAW MATERIAL
Product Name Raw Material Name KG/KG KG/MONTH
Group – I
isopropyl alcohol Hcl 0.92 1840.00
Ranney nickel (10%
charcoal)
0.12 240.00
Anhydrous aluminum
chloride
0.06 120.00
Ethyl acetate 2.33 4660.00
Hydrochloric acid 0.29 580.00
Hydrogen gas 0.01 20.00
Hyflowsuper cell 0.01 20.00
Isopropyl alcohol 14.17 28340.00
Liquid bromine 0.68 1360.00
Methanol 8.33 16660.00
M-hydroxy acetophenone 1.17 2340.00
N-methyl benzyl amine 0.86 1720.00
Phenylephrine hcl
Toluene 2.33 4660.00
Quinolic Acid 1.25 2500.00
N-methyl Piperazine 0.90 1800.00
Butanol 1.00 2000.00
Acetic Acid 0.30 600.00
Ofloxacin
Liquid Ammonia 0.45 900.00
Methyl piperazinyl 1.07 2140.00
4-chloro 2-methyl 10h-
thieno [2,3b][1,5]
benzodiazepine
1.33 2660.00
N N Dimethyl amine 5.33 10660.00
Olanzapine
Acetonitrile 4.00 8000.00
5-Chloro Aniline 2-4
Disulfonamide
1.20 2400.00
Sulphuric acid 0.16 320.00
Methanol 0.39 780.00
Formaldehyde 0.10 200.00
Sodium hydroxide 0.05 100.00
Hydrochloric acid 0.14 280.00
Hydrochlorothiazide
Activated carbon 0.01 20.00
5H-Dibenz [b,f]azepine-5-
carbonitrile
1.35 2700.00
Sodium nitrite 0.68 1360.00
Acetic acid 1.95 3900.00
Iron 0.08 160.00
Boron TriFluoride 0.35 700.00
Oxcarbazepine
IsoPropylAmine 2.25 4500.00
10-Methoxy-5H-
dibenz[b,f]azepine-5-
5H-Dibenz [b,f]azepine-5-
carbonitrile 1.23
2460.00
Page 19 of 177
Sodium nitrite 0.62 1240.00 carbonylchloride, 10-
Methoxyiminostilbene-5-
carbonylchloride
Acetic acid
1.70
3400.00
2,6 Dichlorophenol 0.62 1240.00
Sodium Methoxide
soln.25%
1.46 2920.00
Ethyl Chloro Acetate 0.44 880.00
Aniline 0.34 680.00
Caustic Lye 0.22 440.00
Chloro Acetyl Chloride 0.58 1160.00
Ethoxy ethanol 2.20 4400.00
Aluminum Chloride 0.66 1320.00
Sodium Hydroxide 0.30 600.00
Diclofenac sodium
Activated Carbon 0.01 20.00
2,6 Dichlorophenol 0.77 1540.00
Sodium Methoxide soln.25% 1.82 3640.00
Ethyl Chloro Acetate 0.55 1100.00
Aniline 0.42 840.00
2,6 – dichloro diphenyl amine
(dcdpa)
Caustic Lye 0.28 560.00
2,6 Dichlorophenol 0.62 1240.00
Sodium Methoxide soln.25% 1.46 2920.00
Ethyl Chloro Acetate 0.44 880.00
Aniline 0.34 680.00
Caustic Lye 0.22 440.00
Chloro Acetyl Chloride 0.58 1160.00
N-chloroacetyl-n-phenyl-2,6-
dichloro aniline (cpdca)
Ethoxy ethanol 2.20 4400.00
2,6 Dichlorophenol 0.62 1240.00
Sodium Methoxide soln.25% 1.45 2900.00
Ethyl Chloro Acetate 0.43 860.00
Aniline 0.33 660.00
Caustic Lye 0.22 440.00
Chloro Acetyl Chloride 0.58 1160.00
Ethoxy ethanol 2.20 4400.00
Indolenone
Aluminium Chloride 0.66 1320.00
2,3 Lutidine 0.51 255.00
Acetic acid 0.51 255.00
Hydrogen peroxide 0.37 185.00
Nitric acid 0.33 165.00
Sulfuric acid 1.2 600.00
3-Methoxy-1-propanol
Acetic anhydride
0.44 220.00
Sodium hydroxide 0.42 210.00
Toluene 10.55 5275.00
Dimethyl Sulphoxide 2.22 1110.00
Acetic anhydride 1.67 835.00
2-Hydroxymethyl-3-methyl-4-
(3-methoxy
propanoxyl)pyridine HCL
Hydrochloric acid 0.22 110.00
Page 20 of 177
Methanol 0.72 360.00
4Hydroxy Coumarin 0.92 460.00
Hydroxylamine hydrochloride 1.37 685.00
Potassium acetate 1.93 965.00
Sodium hydroxide 0.09 45.00
Methylene Dichloride 2.29 1145.00
1,2-benisoxazole-3-acetica acid
Hydrochloric Acid 0.47 235.00
Cis-BromoBenzoate 1.30 3250.00
Imidazole 1.16 2900.00
Dimethylformemide(DMF) 0.06 150.00
Toluene 3.80 9500.00
Sodium Bicarbonate 0.25 625.00
Sodium hydroxide 0.20 500.00
Hydro chloric acid 0.28 700.00
Ethyl Acetate 2.85 7125.00
Activated Carbon 0.01 25.00
Vacuum Salt 0.01 25.00
Methylene chloride 5.36 13400.00
P-Toluene Sulfonyl Chloride 0.78 1950.00
Sodium Carbonate 0.52 1300.00
Cis-tosylate
Methanol 2.37 5925.00
(2R-trans)-5-(4-
Fluorophenyl)-2-(1-
Methyl)-N,4diphenyl-1-[2-
Tetra hydroxy-4-hydroxy-
6-Oxo-2H-pyran-2yl)ethyl]-
1H-pyrrole-3-carboxamide
1.91 4775.00
Isopropyl Amine 3.98 9950.00
Sodium Hydroxide 0.31 775.00
Atorvastatin calcium
Calcium Acetate solution 1.40 3500.00
(2R-trans)-5-(4- Fluorophenyl)
2-(1-
Methyl)-N,4diphenyl-1-[2-
Tetra
hydroxy-4-hydroxy- 6-Oxo-2H
pyran-2-
yl)ethyl]- 1H-pyrrole-3-
carboxamide
1.90 4750.00
Iso Propyl Alcohol 2.23 5575.00
Sodium Hydroxide 0.31 775.00
tert-Butyl (4R,6R)-2-[[[6-(2-4-
fluorophenyl)-5-isopropyl-3-
phenyl-4-
(phenylcarbamoyl)pyrrol-1-
yl]ethyl]-2,2-dimethyl-1,3-
dioxan-4-yl]acetate
Calcium Acetate solution 1.39 3475.00
Benzopyran-2-
Carboxaldehyde Derivative
1.40 3500.00
Trimethylsulfoxonium
iodide
1.15 2875.00
Potassium hydroxide 0.56 1400.00
Nebivolol Hydrochloride
Benzyl amine 0.40 1000.00
Page 21 of 177
Toluene 3.00 7500.00
Ammonium formate 0.60 1500.00
Hydrogen gas 0.01 25.00
Methanol 5.20 13000.00
10% Sodium Hypochlorite 2.79 6975.00
Acetone 6.23 15575.00
Diflouro methoxy-2-MB 0.73 1825.00
Iso Propyl Acetate 11.54 28850.00
Sodium Hydroxide 0.41 1025.00
Pantoprazole chloro
compound
0.77 1925.00
Pantaprazol Sodium
Pantoprazole sulfide 1.15 2875.00
Pantoprazole chloro compound0.67 1675.00
Diflouro Methoxy-2-MB 0.64 1600.00
Sodium Hydroxide 0.26 650.00
5-(Difluoromethoxy)-2- {[(
3,4Dimethoxypyridin - 2-yl)
methyl]thio}-1H-
benzimidazolee Iso propyl alcohol 4.02 10050.00
1,3-Dichloro acetone 0.63 1575.00
Guanylthiourea 0.56 1400.00
Potassium Iodide 0.02 50.00
N-((4-Chloromethyl)-2-
Thiozolyl)Guanidine
Hydrochloride
Acetone 1.91 4775.00
Methyl aceto acetate 1.14 3990.00 Methyl 3-amino-2 butenoate
Liq ammonia 2.75 9625.00
1,3-Difluorobenzene 0.55 1925.00
Aluminium Chloride 0.65 2275.00
Methylene Chloride 3.25 11375.00
Chloroacetyl chloride 0.57 1995.00
4-Amino-1,2,4-Triazole 0.44 1540.00
Iso Propyl Alcohol 2.14 7490.00
Hydrochloric acid 0.20 700.00
Sodium Nitrite 0.32 1120.00
Hydrochloric acid 0.68 2380.00
Ammonia Solution 0.55 1925.00
2,4-Difluoro-2-(1h- 1,2,4-
Triazole-1-Yl) Acetophenone
(Dfta)
Sodium bicarbonate 0.04 140.00
Cis-Bromobenzoate 1.10 3850.00
1H,1,2,4-Triazole 0.70 2450.00
Potassium carbonate 1.05 3675.00
Dimethyl formamide 1.85 6475.00
Sodium hydroxide 0.17 595.00
Toluene 1.56 5460.00
Triethyl amine 0.40 1400.00
Methane sulfonyl chloride 0.38 1330.00
Methylene chloride 1.92 6720.00
cis-2-(2,4-Dichlorophenyl)-2-
(1H-1,2,4-triazol-1-ylmethyl)-
1,3-dioxolan-4-ylmethyl
methane sulphonate
Activated Carbon 0.04 140.00
1-(4-Methyxy) piperadine 0.66 2310.00
Paranitrochlorobenzene 0.54 1890.00
1-(4-Methoxyphenyl)-4-(4-
nitrophenyl) piperazine
Potassium carbonate 0.58 2030.00
Page 22 of 177
Dimethyl formamide 0.76 2660.00
Methanol 1.53 5355.00
Acetone 1.55 5425.00
Carbon 0.01 35.00
4- (2- Methoxyethyl) Phenol 0.80
2800.00
Epichlorohydrine 0.80 2800.00
2-[[4-(2-
Methoxyethyl)phenoxy]methyl-
oxirane Sodium hydroxide 0.24 840.00
4-(4-phenylbutoxy)benzoic acid0.80 2800.00
1-(3-amino-2-hydroxyphenyl)
Ethanone
0.46 1610.00
Methylene Dichloride(F/R) 4.70 16450.00
Dimethyl Formamide 0.04 140.00
Thionyl Chloride 0.47 1645.00
Pyridine 0.71 2485.00
Hydrochloric acid 2.40 8400.00
3''-acetyl-2''-hydroxy-4-(4
phenylbutoxy) benzanilide
Sodium Bicarbonate 0.24 840.00
2-Bromo-1-cyclopropyl-2-
(2 flourophenyl)ethanone
0.88 2200.00
5,6,7,7a-tetrahydrothieno
[3,2-c]pyridine-2-(4H)-one
0.54 1350.00
Potassium Hydroxide 0.22 550.00
Methanol 8.76 21900.00
Acetic anhydride 0.32 800.00
Methyl ethyl ketone 2.94 7350.00
Hydrochloric Acid 0.10 250.00
Prasugrel Hydrochloride
Acetone 3.12 7800.00
2-Bromo-1-cyclopropyl-2-(2-
flourophenyl)ethanone
0.90 2250.00
5,6,7,7a-tetrahydrothieno[3,2
c]pyridine-2-(4H)-one
0.55 1375.00
Potassium Hydroxide 0.23 575.00
5-[2-Cyclopropyl-1-(2-
fluorophenyl)-2-oxoethyl] -
5,6,7,7a-tetrahydrothieno[3,2-
c]pyridin-2(4H)-one
Methanol 2.70 6750.00
3-[(1-Methyl-2-{[4-(5-oxo-
4,5-dihydro-
[1,2,4]oxadiazol-3-yl)-
phenylamino]-methyl)-1H
benzoimidazole-
5carbonyl)-pyridin-2-
ylamino]- propionic acid
ethyl ester
0.97 2425.00
P-toluene sulphonic acid 0.25 625.00
Acetic acid 0.20 500.00
Ethanol 25.00 62500.00
Hexachloroformate 0.28 700.00
Acetone 12.00 30000.00
Dabigatran
Potassium Hydroxide 0.09 225.00
Page 23 of 177
Hydrochloric acid 0.00 20.00
1,3-Dichloro acetone 0.53 1325.00
Guanylthiourea 0.50 1250.00
Potassium Iodide 0.02 50.00
Acetone 1.70 4250.00
Thiurea 0.25 625.00
Sodium Hydroxide 0.40 1000.00
N-Sulfamyl-3-chloro
propionamidineHCl
0.74 1850.00
Acetic acid 0.25 625.00
Methanol 34.36 85900.00
Ammonia (23%) 0.24 600.00
Femotidine
Activated carbon 0.06 150.00
L-Valine 0.50 1250.00
Thionyl Chloride 0.50 1250.00
Methanol 8.89 22225.00
Toluene 12.22 30550.00
4-Bromomethyl-biphenyl-2-carbonitrile 0.91
2275.00
N-[(2'-Cyano[1,1'-biphenyl]-4-
yl)methyl]-L valine methyl ester
Potassium carbonate 0.50 1250.00
Acetic Acid 0.43 1505.00
Benzene Sulfonic Acid 0.64 2240.00
Ethyl acetate 0.14 490.00
Ethyl Chloroaceto acetate 0.55 1925.00
Hydrochloric Acid 0.05 175.00
Haxene 0.22 770.00
Liq. Ammonia 0.96 3360.00
Methanol 0.05 175.00
Methyl aceto acetate 0.50 1750.00
Mono Methyl Amine 3.75 13125.00
Monoethanol amine 0.45 1575.00
Ortho Chlorobenzaldehyde 0.40 1400.00
Phthalic anhydride 1.00 3500.00
Piperidine 0.02 70.00
Sodium chloride 0.50 1750.00
Sodium hydride 0.28 980.00
Amlodipinbesylate
Toluene 0.23 805.00
Phthalic anhydride 1.00 3500.00
Mono ethanol amine 0.45 1575.00
Toluene 9.11 31885.00
Methyl aceto acetate 0.40 1400.00
Liq ammonia 0.96 3360.00
Ethyl Chloroaceto acetate 0.55 1925.00
Hydrochloric Acid 0.05 175.00
Acetic acid 0.43 1505.00
Sodium chloride 0.50 1750.00
Amlodipine base
Sodium hydride 0.28 980.00
Page 24 of 177
Ortho Chlorobenzaldehyde 0.40 1400.00
Hexane 1.91 6685.00
Piperidine 0.02 70.00
Ethyl acetate 35.0 122500.00
Hexane 35.6 124600.00
Mono Methyl Amine 37.5 131250.00
1-(4-Methyxy) piperadine 1.12 3920.00
Paranitrochlorobenzene 0.92 3220.00
Potassium carbonate 1.64 5740.00
Dimethyl formamide 13.93 48755.00
Methanol 2.60 9100.00
Acetone 2.63 9205.00
Carbon 0.02 70.00
Palladium carbon 0.01 35.00
Hydrogen gas 0.13 455.00
Phenyl chloroformate 1.01 3535.00
Sodium bicarbonate 0.91 3185.00
Methylene chloride 3.15 11025.00
Hydragin hydrate 0.84 2940.00
n-Butanol 1.88 6580.00
Formamidine acetate 0.82 2870.00
2-Bromo butane 1.60 5600.00
Hydrochloric acid 0.49 1715.00
Hydrobromic acid 12.32 43120.00
2,4-dihydro-4-[(4-(4-
hydroxyphenyl)-1-
piperazinyl)phenyl]-2-(1-
methylpropyl)-3h-1,2,4-triazole-
3-one
Sodium carbonate 1.12 3920.00
4- (2- Methoxyethyl)
Phenol
0.89 3115.00
Epichlorohydrine 0.89 3115.00
Sodium hydroxide 0.27 945.00
Mono isopropyl amine 2.68 9380.00
Toluene 3.57 12495.00
Hydrochloric Acid 0.54 1890.00
Caustic lye 0.27 945.00
Ethyl Acetate 3.57 12495.00
Tartaric Acid 0.24 840.00
Metoprolol tartrate
Methanol 0.63 2205.00
4- (2- Methoxyethyl) Phenol 0.67
2345.00
Epichlorohydrine 0.67 2345.00
Sodium Hydroxide 0.20 700.00
Mono isopropyl amine 2.02 7070.00
Toluene 2.69 9415.00
Hydrochloric acid 0.40 1400.00
1-(Isopropylamino)-3-[4-(2-
methoxyethyl) phenoxy]-2-
propanol
Caustic lye 0.20 700.00
4- (2-Methoxyethyl) Phenol 0.89 3115.00
Epichlorohydrine 0.89 3115.00
Metoprolol succinate
Sodium hydroxide 0.27 945.00
Page 25 of 177
Mono isopropyl amine 2.68 9380.00
Toluene 3.57 12495.00
Hydrochloric Acid 0.54 1890.00
Caustic lye 0.27 945.00
Ethyl Acetate 3.57 12495.00
Succinic Acid 0.19 665.00
Methanol 0.63 2205.00
Cis-BromoBenzoate 1.53 3825.00
Imidazole 1.36 3400.00
Dimethylformemide(DMF) 0.07 175.00
Toluene 4.46 11150.00
Sodium Bicarbonate 0.29 725.00
Sodium hydroxide 0.90 2250.00
Hydrochloric Acid 0.31 775.00
Ethyl Acetate 7.70 19250.00
Vacuum Salt 0.01 25.00
PeraHydroxy phenyl n-
acetyl piperazine
0.56 1400.00
Dimethyl Sulfoxide 1.66 4150.00
Sodium methoxide powder 0.14 350.00
Acetone 0.67 1675.00
Methanol 0.92 2300.00
Ketoconazole
Activated Carbon 0.05 125.00
Phthalic anhydride 0.67 2345.00
Mono ethanol amine 0.30 1050.00
Toluene 6.07 21245.00
Methyl aceto acetate 0.27 945.00
Liq ammonia 0.64 2240.00
Ethyl Chloroaceto acetate 0.37 1295.00
Hydrochloric Acidl 0.03 105.00
Acetic acid 0.29 1015.00
Sodium chloride 0.33 1155.00
Sodium hydride 0.19 665.00
Ortho Chlorobenzaldehyde 0.27 945.00
Hexane 1.28 4480.00
Piperidine 0.01 35.00
Ethyl acetate 2.34 8190.00
Phthaloyl amlodipine
Hexane 2.38 8330.00
1-(4-Methyxy) piperadine 0.94 3290.00
Paranitrochlorobenzene 0.77 2695.00
Potassium carbonate 1.38 4830.00
Dimethyl formamide 11.70 40950.00
Methanol 2.19 7665.00
Acetone 2.22 7770.00
Carbon 0.02 70.00
2,4-Dihydro-4-[4-[4-(4-
methoxyphenyl)-1-
piperazinyl]phenyl]-2-(1-
methylpropyl)-3H-1,2,4-triazol-
3-one
Palladium carbon 0.01 35.00
Page 26 of 177
Hydrogen gas 0.11 385.00
Phenyl chloroformate 0.85 2975.00
Sodium bicarbonate 0.76 2660.00
Methylene chloride 2.65 9275.00
Hydragin hydrate 0.69 2415.00
n-Butanol 1.59 5565.00
Formamidine acetate 0.69 2415.00
2-Bromo butane 1.34 4690.00
Hydrochloric acid 0.41 1435.00
Acetic acid 0.43 1075.00
Acetone 10.67 26675.00
Activated Carbon 0.10 250.00
Di isopropyl ethylamine 0.04 100.00
Hydrochloric acid 0.37 925.00
Methylene Dichloride
(MDC)
12.00 30000.00
Methane sulfonyl chloride 0.10 250.00
Methanol 14.80 37000.00
N-vinyl pyrolidone 0.72 1800.00
Sodium chloride 0.80 2000.00
Sodium hydroxide 0.58 1450.00
Tertiary Butyl amine 0.20 500.00
Thiol Acetic acid 0.49 1225.00
Thiophene-2-ethylamine 2.32 5800.00
Montelukast sodium
Toluene 48.00 120000.00
L-Valine 0.45 1125.00
Thionyl Chloride 0.46 1150.00
Methanol 8.00 20000.00
Toluene 25.00 62500.00
4-Bromomethyl-biphenyl-
2-carbonitrile
0.82 2050.00
Potassium carbonate 0.45 1125.00
Valeryl Chloride 0.34 850.00
Tri Ethyl Amine 0.20 500.00
Sodium Azide 0.16 400.00
Sodium Bicarbonate 0.25 625.00
Sodium Sulphate 0.10 250.00
Tri Butyl tin Chloride 0.80 2000.00
Hydrogen Gas 0.01 25.00
Sodium Hydroxide 0.20 500.00
Xylene 2.40 6000.00
Methylene Dichloride 5.00 12500.00
Acetic acid 0.40 1000.00
N-Hexane 2.00 5000.00
Valsartan
Activated Carbon 0.10 250.00
Venlafaxine Hydrochloride 4-Methoxy Benzoyl Cyanide 0.97 2425.00
Page 27 of 177
Methanol 3.50 8750.00
Sodium Methoxide 0.91 2275.00
Cyclohexanone 0.90 2250.00
Toluene 4.81 12025.00
Acetic Acid 8.15 20375.00
Tetra butyl ammonium
bromide
0.05 125.00
Sodium hydroxide 4.77 11925.00
formic soda 1.94 4850.00
Formaldehyde 1.12 2800.00
Hydrochloric acid 2.51 6275.00
Ethyl acetate 22.53 56325.00
Sodium Sulphate 0.27 675.00
Sodium chloride 0.34 850.00
Hyflowsupercell 0.04 100.00
IsoPropylAlcohol 14.6 36500.00
IsoPropyl Alcohol HCl 1.09 2725.00
Activated Charcoal 0.01 25.00
1-[((4
Chlorophenyl)phenyl)methyl]
-4-
[(phenylsulphonyl)]piperazine
0.92 22300.00
2(2-Chloroethoxy )acetamide 0.29 725.00
4-Hydroxy benzoic acid 0.32 800.00
Hydrobromic acid 0.17 425.00
Sodium hydroxide 0.17 425.00
Hydrochloric acid 0.31 775.00
Sodium carbonate 0.23 575.00
Potassium iodide 0.03 75.00
Toluene 30.30 75750.00
Methylene Dichloride 37.20 93000.00
Acetone 9.30 23250.00
LevocetirizineDihydrochloride
Activated carbon 0.08 200.00
Sodium Hydroxide 1.90 4750.00
R-(-)-3- (Carbamoyl
methyl)-5-methyl hexanoic
acid
1.37 3425.00
Liquid Bromine 1.23 3075.00
Hyflosupercell 0.07 175.00
Activated carbon 0.02 50.00
Hydrochloric acid 2.46 6150.00
Pregabalin
Iso Propyl Alcohol 7.06 17650.00
Catechol 0.92 2300.00
Sodium Hydroxide 0.76 1900.00
Dimethyl Sulphate 2.30 5750.00
Veratric Acid
Aluminium Chloride 1.32 3300.00
Page 28 of 177
Acetyl Chloride 1.04 2600.00
Methylene Dichloride 5.74 14350.00
Hydrochloric Acid 3.00 7500.00
Sodium Hypo Chlorite 12.30 30750.00
Activated Carbon 0.02 50.00
Sodium meta bi sulphate 0.07 175.00
Sodium Bicarbonate 0.02 50.00
1,2,4-Triazole 0.66 2310.00
1,3-Diflurobenzene 0.80 2800.00
4-amino-1,2,4-Triazole 0.65 2275.00
Aluminum Chloride 0.96 3360.00
Ammonia Solution 3.36 11760.00
Activated Carbon 0.06 210.00
Chloroacetyl Chloride 0.84 2940.00
Citric acid 0.06 210.00
Hydrochloric Acid 2.02 7070.00
Hyflowsupercell 0.05 175.00
IsoPropylAlcohol 3.16 11060.00
Methylene Chloride 4.80 16800.00
Potassium Hydroxide 0.94 3290.00
Sodium bicarbonate 0.06 210.00
Sodium Nitrite 0.47 1645.00
Toluene 8.40 29400.00
Fluconazole
Trimethylsulphoxonium
iodide
1.32 4620.00
1-(4-MethyxyPhenyl)
piperazine
1.02 3570.00
1H,1,2,4-Triazole 0.83 2905.00
2-Bromo butane 0.39 1365.00
Acetone 0.06 210.00
Activated Carbon 0.09 315.00
Cis-Bromobenzoate 1.31 4585.00
Dimethyl formamide 0.52 1820.00
Ethyl acetate 0.14 490.00
Formamidine acetate 0.75 2625.00
Hydragin hydrate 0.76 2660.00
Hydrobromic acid 0.31 1085.00
Hydrochloric acid 0.45 1575.00
Hydrogen gas 0.12 420.00
Hyflowsupercell 0.08 280.00
Methane sulfonyl chloride 0.45 1575.00
Methanol 0.30 1050.00
Methylene chloride 0.15 525.00
n-Butanol 0.03 105.00
Palladium carbon 0.00 35.00
Itraconazole
Paranitrochlorobenzene 0.84 2940.00
Page 29 of 177
Phenyl chloroformate 0.92 3220.00
Potassium carbonate 2.75 9625.00
Potassium hydroxide 0.61 2135.00
Sodium carbonate 1.02 3570.00
Sodium bicarbonate 0.84 2940.00
Sodium hydroxide 0.21 735.00
Toluene 0.11 385.00
Triethyl amine 0.47 1645.00
4-Chloro
benzhydrylpiperazine
0.92 3220.00
Toluene 8.20 28700.00
2-Chloroethanol 0.46 1610.00
Triethylamine 1.00 3500.00
Sodium carbonate 0.40 1400.00
Sodium monochloro acetate 0.70 2450.00
Potassium hydroxide 0.34 1190.00
Dimethylformamide 0.20 700.00
Methylene dichloride 3.00 10500.00
Acetone 3.00 10500.00
Hydrogen chloride 0.52 1820.00
Cetirizine Dihydrochloride
Activated carbon 0.15 525.00
2,3 Lutidine 0.46 230.00
Acetic acid 0.46 230.00
Hydrogen peroxide 0.33 165.00
Nitric acid 0.30 150.00
Sulfuric acid 1.08 540.00
3-Methoxy-1 -propanol
Acetic anhydride
0.40 200.00
Sodium hydroxide 0.67 335.00
Toluene 13.5 6750.00
Dimethyl Sulphoxide 2.00 1000.00
Acetic anhydride 1.50 750.00
Hydrochloric Acid 0.20 100.00
Thionyl chloride 0.53 265.00
Sodium sulphate 0.10 50.00
Methylene Dichloride 13.50 6750.00
2-mercapto benzimidazole 0.53 265.00
Sodium hypochlorite (8%) 3.27 1635.00
Acetone 1.50 750.00
Sodium Hydro Sulphate 0.12 60.00
Mono Methyl Amine in
Methanol
0.10 50.00
Isopropyl Alcohol 3.00 1500.00
Rabeprazole sodium
Activated Carbon 0.10 50.00
Pranklukast 4-(4-phenylbutoxy) benzoic
acid 1.00 3500.00
Page 30 of 177
1-(3-amino-2-hydroxyphenyl)
ethanone 0.58 2030.00
Methylene Dichloride 5.88 20580.00
Dimethyl Formamide 0.05 175.00
Thionyl Chloride 0.59 2065.00
Pyridine 0.90 3150.00
Hydrochloric acid 3.00 10500.00
Sodium Bicarbonate 0.30 1050.00
Sulfuric Acid 5.00 17500.00
Ethyl Acetate 9.00 31500.00
Methanol 1.22 610.00
4HydroxyCoumarin 1.56 780.00
Hydroxylamine hydrochloride 2.34 1170.00
Potassium acetate 3.30 1650.00
Sodium Hydroxide 0.16 80.00
Methylene dichloride 3.92 1960.00
Hydrochloric Acid 0.80 400.00
Ethylene dichloride 6.85 3425.00
1,4 Dioxane 0.78 390.00
Chlorosulfonic acid 0.96 480.00
Sodium Sulphate 0.62 310.00
Toluene 2.40 1200.00
Phosphorus Oxychloride 0.16 80.00
Ammonia Gas 1.04 520.00
Ethyl Acelate 11.56 5780.00
Activated Carbon 0.06 30.00
Zonisamide
Hyflowsupercell 0.06 30.00
Acetone 1.34 3350.00
Acetic acid 2.14 5350.00
Activated carbon 0.06 150.00
Bibenzimidazole 0.85 2125.00
Bromo methyl ester 0.85 2125.00
Celite 0.04 100.00
Dimethyl formamide 8.60 21500.00
Methanol 29.38 73450.00
Potassium hydroxide 0.35 875.00
Sodium hydroxide 0.15 375.00
Telmisartan
Recoveries (-) Acetone 1.27 3175.00
4-Fluoro benzaldehyde 0.52 260.00
4-Methyl-3-oxo-pentanoic
acid ethyl ester
0.66 330.00
Potassium hydroxide 0.24 120.00
Methyl Iodide 0.60 300.00
Methanol 5.50 2750.00
S-Methyl isothio urea 0.35 175.00
Rosuvastatine calcium
2,3-Dichloro-5,6-dicyano 0.85 425.00
Page 31 of 177
benzoquinone
Hexamethylphosphoramide 1.00 500.00
Methylene dichloride 8.00 4000.00
Meta chloroperoxy benzoic
acid
1.19 595.00
Methyl amine 0.10 50.00
Ethanol 2.50 1250.00
Methane sulfonyl chloride 0.35 175.00
Sodium hydride (60%) 0.01 5.00
Di methoxy ethane 3.00 1500.00
Hydrogen gas 0.01 5.00
Diisobutylaluminium hydride 0.01 5.00
Toluene 8.00 4000.00
Methyl(3R)-3-(tert butyl di
methyl silyloxy)-5-oxo-6- tri
phenyl
phosphoranylidenehexanoate
1.45 725.00
Triethyl amine 0.15 75.00
N,N-Dimethyl formamide 3.00 1500.00
Hydrogen fluoride 0.05 25.00
Tetra Hydro Furan 2.50 1250.00
Ethyl acetate 10.50 5250.00
Diethyl methoxyborane 0.20 100.00
Sodium boro hydride 0.01 5.00
Calcium chloride 0.13 65.00
4-Hydroxyphenyl-
piperazinyltriazolone
1.40 2100.00
(5R,Cis)-toluene-4-sulfonic
acid-5-(2,4-difluorophenyl)-5-
(1H-1,2,4-triazol-1-yl)methyl
tetrahydrofuran-3-yl
methylester
1.40 2100.00
Sodium Hydroxide 0.90 1350.00
Hydrochloric Acid 0.80 1200.00
Sodium Chloride 1.40 2100.00
Ethyl Acetate 14.00 21000.00
Dimethyl Sulfoxide 11.00 16500.00
Isopropyl Alcohol 83.00 1124500.00
Hydrogen gas 0.05 75.00
Methanol 23.00 34500.00
Acetone 19.00 28500.00
Palladium Carbon 0.90 1350.00
Posaconazole
Methylene Dichloride 9.00 13500.00
Chenodeoxycholic acid 2.75 4125.00
Acetone 90.70 136050.00
N-Bromosuccinamide 2.24 3360.00
Ursodiol
Potassium tertbutoxide 2.44 3360.00
Page 32 of 177
Ranney Nickel 0.96 1440.00
Ethyl acetate 8.08 12120.00
Isopropyl alcohol 34.20 51300.00
Hydrochloric Acid 2.10 3150.00
Triethylamine 0.55 825.00
Page 33 of 177
ANNEXURE - III
___________________________________________________________________________
BRIEF MANUFACTURING PROCESS DESCRIPTION
Group – I
1. Phenylephrine HCl
Process Description:
M-hydroxyacetophenone reacts with bromine in presence of aluminium chloride to form M-
hydroxyl bromoacetophenone which will react with N-methyl benzyl amine in presence of
Ranney Nickel to obtain phenylephrine hydrochloride.
Route of Synthesis:
Page 34 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) m-hydroxyacetophenone 350 Stage- I Mass 500 Ethyl acetate 700 HBr 210
An.Aluminium chloride 17.5 Solvent Liq. Bromine 204 Toluene recovery 665 Toluene 700 Toluene loss 21 n-methyl benzyl amine 258 Ethyl acetate recovery 665 Water 250 Ethyl acetate loss 21
Acidic isopropyl alcohol 75 Liquid waste
Water 250
Aluminum chloride 17.5
Toluene 14
Ethyl acetate 14
Acidic Isopropyl alcohol 75
Solid waste 0
Gaseous waste 0
Organic residue 102 Total 2554.5 Total 2554.5
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Stage- I Mass 500 Stage- II mass 400
Methanol 2500 Solvent Ranney nickel (10% charcoal) 25 Methyl recovery 2250 Hydrogen gas 2 Methyl loss 125
Hyflow powder 2 Liquid waste Water 250 Water 250
Methanol 63
Organic 92
Solid waste 99
Gaseous waste 0
Organic residue 0 Total 3279.0 Total 3279.0
Stage-III
Input QTY.(kgs) Output QTY.(kgs) Stage- II Mass 400 Stage- III Mass 375
Isopropyl alcohol 2000 Solvent HCl 88 Isopropyl alcohol recovery 1800 water 250 Isopropyl alcohol loss 100
Acidic isopropyl alcohol 200 Liquid waste
Water 250
Isopropyl alcohol 100
Acidic isopropyl alcohol 200
Solid waste 113
Gaseous waste 0
Page 35 of 177
Organic residue 0 Total 2938.0 Total 2938.0
Stage-IV
Input QTY.(kgs) Output QTY.(kgs)
Stage- III Mass 375 Phenylephrine HCL -Product 300
Isopropyl alcohol 2250 Solvent Activated charcoal 12 Isopropyl alcohol recovery 1800 Hyflow powder 2 Isopropyl alcohol loss 112.5
Liquid waste 0
Solid waste 351.5
Gaseous waste 0
Organic residue 75 Total 2639.0 Total 2639.0
Page 36 of 177
2. Ofloxacin Process Description:
Quonalinic acid & N- methyl piperizine reacted in butanol. The reaction mass acetic acid is
added mass is neutralized to give ofloxacin. Purified, filtered & dried to give ofloxacin.
Route of Synthesis:
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) Quinolic Acid 125.00 Ofloxacin 100.00 N-methyl Piperazine 90.00 Butanol Rec 95.00 Butanol 100.00 Dry loss 20.00 Acetic Acid 30.00 Solvent Loss 05.00 Liq Ammonia 45.00 Aqu effluent 170.00 Total 390.00 Total 390.00
Page 37 of 177
3. Olanzapine
Process Description:
Charge Methyl piperazinylChloro-thieno benzodiazepine, N N DMA, catalyst heat and reflux distilled out. Add Acetonitrile cool & filters dry in RCVD to get Olanzapine.
Route of Synthesis:
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs)
Methyl piperazinyl 80.00 Olanzapine 75.00 Chloro-thieno benzodiazepine 100.00 Aqu. Effluent 280.00 N N DMA 400.00 Process loss 25.00 Catalyst 10.00 Solvent Recovery 510.00
Acetonitrile 300.00
Total 890.00 Total 890.00
Page 38 of 177
4. Hydrochlorothiazide
Process description:
5-Chloro Aniline 2-4 Disulphonamide in water reacted with Formaldehyde at 80°C gives
Hydrochlorothiazide. Centrifuge the reaction mass, Give charcoal treatment and filter, dry
the material.
Route of Synthesis:
Material balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
5-Chloro Aniline 2-4 Disulphonamide 240 Hydrochlorothiazide 200
Sulphuric acid 32.2 Activated carbon 3.5
Methanol 79.2 Effluent 570.5
Formaldehyde 20.4
Sodium hydroxide 10
Hydrochloric acid 28.7
Activated carbon 3.5
Purified water 360
Total 774 Total 774
Page 39 of 177
5. Oxcabazepine
Process Description:
5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid &
Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from
IPA, filtered & dried to give Oxcabazepine.
Route of Synthesis:
Page 40 of 177
Material balance:
Stage-I Input QTY.(kgs) Output QTY.(kgs) 5H-Dibenz [b,f]azepine-5- carbonitrile 135.00 Stage-1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00
Acetic acid 185.00 Total 388.00 Total 388.00
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Stage -1 109.00 Stage-1 87.00
Iron 8.00 Aqu. Effluent for Fe Acetate 175.00
Acetic acid 110.00
Boron TriFluoride 35.00
Total 262.00 Total 262.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs) Stage -2 87.00 Oxcabazepine 100.00 IPA 225.00 IPA Rec 202.00
Dry Loss 10.00 Total 312.00 Total 312.00
Page 41 of 177
6. 10-Methoxy-5H-dibenz[b,f]azepine-5-carbonylchloride, 10-
Methoxyiminostilbene-5-carbonylchloride
Process Description:
5H-Dibenz[b,f]azepine-5- carbonitrile ; Sodium nitrite treated in presence of Acetic acid &
Iron Boron Trifluoride is added. The mass is filtered to give crude product, crystallized from
IPA, filtered & dried to give Oxcabazepine.
Flow Chart:
Material balance:
Stage-I Input QTY.(kgs) Output QTY.(kgs) 5H-Dibenz [b,f]azepine-5- carbonitrile 135.00 Stage-1 109.00 Sodium nitrite 68.00 Aqu. Effluent for Sodium nitrite 279.00
Acetic acid 185.00 Total 388.00 Total 388.00
5H-Dibenz [b,f]azepine-5-
carbonitrile
Sodium nitrite
Acetic acid
Iron
Acetic acid
Boron Trifluoride
Stage-1
10-Methoxy-5H-dibenz [b,f]azepine-5-
carbonylchloride, 10-Methoxyiminostilbene-5-
carbonylchloride
Page 42 of 177
7. Diclofenac Sodium
Process Description:
Stage-I:
2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor
inrequiredproportion.The mass is allowed to react together at required temperature and
pressure condition, once the reaction is over, the material is filtered and dried in drier and
packed in drums and stored as DCDPA
Stage-II:
DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel,
hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic
solution in scrubber tower. The material filtered, washed and dried packed and store as
CPDCA
Stage-III:
CPDCA, aluminium chloride to allow react in a reactor and controlled temperature
condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated
during reaction and quenching is taken to scrubber system. Neutralized material is filtered,
washed, dried, packed and store as Indolinone
Stage-IV:
Indolinone, caustic and solvent added reaction vessel, reaction is done under
controlledcondition the material after reaction is over, filtered, and dried packed and stored
as DFS.
Page 43 of 177
Material balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20
Aniline 33.92 Effluent 113.60 Caustic Lye 22.00 Process loss 32.80
Water 122.80
Total 429.60 Total 429.60
Stage-II
Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00
Ethoxy ethanol 220.00 Solvent Reco 235.00
Dry Loss 8.00 Total 358.00 Total 358.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 110.00 Water 83.00 HCL 15.00
Drying Loss 35.60
Total 260.60 Total 260.60
Stage-IV
Input QTY.(kgs) Output QTY.(kgs) Idolinone 109.00 Diclofenac Sodium 100.00 Sodium Hydroxide 30.20 Effluent 69.00 Water 60.00 Charcoal 1.00
Charcoal 0.8 Dry Loss 30.00 Total 200.00 Total 200.00
Page 44 of 177
8. 2,6 – dichloro diphenyl amine (dcdpa)
Process Description:
2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor
inrequiredproportion.The mass is allowed to react together at required temperature and
pressure condition, once the reaction is over, the material is filtered and dried in drier and
packed in drums and stored as DCDPA.
Route of Synthesis:
Material balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20
Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80
Water 192.80
Total 499.60 Total 499.60
Page 45 of 177
9. N-chloroacetyl-n-phenyl-2,6-dichloro aniline (cpdca) Process Description:
Stage-I:
2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor
inrequiredproportion.The mass is allowed to react together at required temperature and
pressure condition, once the reaction is over, the material is filtered and dried in drier and
packed in drums and stored as DCDPA.
Stage-II:
DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel,
hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic
solution in scrubber tower. The material filtered, washed and dried packed and store as
CPDCA.
Route of synthesis:
Page 46 of 177
Material balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20
Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80
Water 192.80
Total 499.60 Total 499.60
Stage-II
Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00
Ethoxy ethanol 220.00 Solvent Reco 235.00
Dry Loss 8.00 Total 358.00 Total 358.00
Page 47 of 177
10. Indolenone
Process Description:
Stage-I:
2,6 DCP, sodium methoxide, ethyl chloro acetate, aniline caustic are added to reactor
inrequiredproportion.The mass is allowed to react together at required temperature and
pressure condition, once the reaction is over, the material is filtered and dried in drier and
packed in drums and stored as DCDPA.
Stage-II:
DCDPA, ethoxy ethanol, chloro acetyl chloride are added to a reaction vessel,
hydrogenchloride gas generated during the reaction is scrubbed off with the help of caustic
solution in scrubber tower. The material filtered, washed and dried packed and store as
CPDCA.
Stage-III:
CPDCA, aluminium chloride to allow react in a reactor and controlled temperature
condition.The mass is then quenched in water and filtered, hydrogen chloride gas generated
during reaction and quenching is taken to scrubber system. Neutralized material is filtered,
washed, dried, packed and store as IndolinoneDiclofenac Sodium (DFS).
Route of Synthesis:
Page 48 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) 2,6 D.C.P 61.76 D.C.D.P.A 80.00 Sodium Methoxide soln.25% 145.60 Solvent Reco 184.00 Ethyl Chloro Acetate 43.52 NaCl 19.20
Aniline 33.92 Effluent 183.60 Caustic Lye 22.00 Process loss 32.80
Water 192.80
Total 499.60 Total 499.60
Stage-II
Input QTY.(kgs) Output QTY.(kgs) D.C.D.P.A 80.00 C.P.D.C.A 100.00 Chloro Acetyl Chloride 58.00 HCL gas 15.00
Ethoxy ethanol 220.00 Solvent Reco 235.00
Dry Loss 8.00 Total 358.00 Total 358.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs) C.P.D.C.A 112.00 Indolinone 100.00 Aluminium Chloride 65.60 Aqu Effluent 150.00 Water 123.00 HCL 15.00
Drying Loss 35.60
Total 300.60 Total 300.60
Page 49 of 177
11. 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl) pyridine HCL
Process Description:
Stage-1 :
2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N- Oxide
it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1.
Stage-2:
Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2
Compound
Stage-3:
Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and Hydrochloric
Acid to get Stage-3 Compound.
Route of Synthesis:
Page 50 of 177
Mass Balance:
STAGE-1
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
2,3 Lutidine 46.00 Stage-1 65.00
Acetic acid 46.00 Spent acid 140.00
Hydrogen peroxide 33.00 Effluent 200.80
Nitric acid 30.00 Organic Residue 7.20
Sulfuric acid 108.00
Water 150.00
Total 413.00 Total 413.00
STAGE-2
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 65.00 Stage-2 80.00
3-Methoxy-1 –propanol
Acetic anhydride
40.00 Toluene Reco 235.00
Sodium hydroxide 18.50 DMSO Reco 188.00
Toluene 250.00 Solvent loss 22.00
DMSO 200.00 Inorganic solid waste 29.70
Organic waste 11.80
Water generate 7.00
Total 573.50 Total 573.50
STAGE-3
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-2 80.00 Stage-3 90.00
Acetic anhydride 150.00 Toluene Reco 660.00
NaOH 20.00 Acetic anhydride Reco 107.00
HCL 20.00 Effluent 160.50
Toluene 700.00 Organic Residue 13.50
Water 100.00 Process loss 39.00
Total 1070.00 Total 1070.00
Page 51 of 177
12. 1,2-benisoxazole-3-acetica acid
Process Description:
Stage-I:
4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate
anhydrous in methanol at desired temperature and appropriate condition.
Route of Synthesis:
Mass Balance:
STAGE-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Methanol 153.00 Stage-1 214.00
4Hydroxy Coumarin 195.30 Methanol Reco 137.7
Hydroxylamine hydrochloride 293.00 Methanol loss 15.3
Potassium acetate 413.00 Effluent 838.30
Sodium hydroxide 20.00 Dry loss 30.00
Methylene Dichloride 290.00 Organic Residue 29.00
Hydrochloric Acid 100.00
Water 300.00
Total 1264.30 Total 1264.30
Page 52 of 177
13. Cis-tosylate Process Description: Stage I:
CBB is reacted with IMD in the presence of DMF as solvent. The reaction mass is quenched in sodium bicarbonate solution and the product is extracted with toluene. The aqueous layer is kept for IMD recovery. The organic layer containing the product is reacted with sodium hydroxide solution. After completion of reaction, the pH of the mass is adjusted with hydrochloric acid. mass is diluted with water and centrifuged. The wet cake is dissolved in ethyl acetate and treated with carbon. The mass is filtered and the ethyl acetate is distilled off. The residue is cooled and centrifuged. The mass is dried to produce KT-I.
Stage II:
KT-I is reacted with PTSC in the presence of sodium carbonate and methylene chloride as
solvent. The reaction mass is diluted and the organic layer separated. Methylene chloride is
distilled off completely from the organic layer and the residue is diluted with methanol and
water. The mass is centrifuges and washed with methanol and water mixture. The mass is
dried to produce Cis-Tosylate (KT-II).
Route of Synthesis:
Page 53 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs)
CBB 780 Stage-1 450
IMD 693.3 IMD Rec 360
DMF 37.2 Toluene Rec 2207.0
Toluene 2275.5 Ethyle Acetate 1620.0
Sodium Bicarbonate 148.2 Aq. Effluent 1599.4
Sodium hydroxide 120.0 Spent carbon 12.0
Water 705.0 Residue 130.0
HCl 156 Process loss 254.9
Ethyl Acetate 1706.4
Activated Carbon 6.0
Vacuum Salt 6.0
Total 6633.3 Total 6633.3
Stage-II
Input QTY.(kgs) Output QTY.(kgs)
Stage-1 450.0 Stage-2 600.0
Methylenechloride 3217.5 Methylenechloride Rec 3024.0
P-Toluene Sulfonyl Chloride 465.0 Methanol Rec 1375.0
Sodium Carbonate 307.5 Aq. Effluent 778.0
HCl 12.0 Process Loss 400
Methanol 1425.0
Water 420
Total 6297.0 Total 6297.0
Page 54 of 177
14. Atorvastatin Calcium Process Description: 2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo-
2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA. The mass is
treated with calcium acetate solution. The crude obtained is crystallized from IPA to give
atorvastatin calcium.
Route of Synthesis:
Page 55 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) Stage - 1 89.00 Aqu. Effluent for IPA Rec 358.00
(2R-trans)-5-(4- Fluorophenyl)-2-(1-
Methyl)-N,4diphenyl-1-[2- Tetra
hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2-
yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00
IPA 225.00
NaOH 31.00
Total 447.00 Total 447.00
Stage-II
Input QTY.(kgs) Output QTY.(kgs)
Stage – 1 89.00 Stage-2 101.00
Calcium Acetate solution 140.00 Aqu. Effluent for Calcium 128.00
Acetate solution Rec
Total 229.00 Total 229.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs)
Stage – 2 101.00 Atorvastatin Calcium 100.00
IPA 173.00 Aqu. Effluent for IPA Rec 155.00
Dry Loss 19.00
Total 274.00 Total 274.00
Page 56 of 177
15. Tert-Butyl (4R,6R)-2-[[[6-(2-4-fluorophenyl)-5-isopropyl-3-phenyl-4-
(phenylcarbamoyl)pyrrol-1-yl]ethyl]-2,2-dimethyl-1,3-dioxan-4-yl]acetate Process Description:
2R-trans)-5-(4-Fluorophenyl)-2-(1-Methyl)-N,4diphenyl-1-[2-Tetra hydroxy- 4hydroxy-6-Oxo-
2H-pyran-2-yl)ethyl]-1H-pyrrole-3-carboxamide treated with NaOH in IPA.
Route of Synthesis:
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) Stage - 1 89.00 Aqu. Effluent for IPA Rec 358.00
(2R-trans)-5-(4- Fluorophenyl)-2-(1-
Methyl)-N,4diphenyl-1-[2- Tetra
hydroxy-4-hydroxy- 6-Oxo-2H-pyran-2-
yl)ethyl]- 1H-pyrrole-3-carboxamide 191.00
IPA 225.00
NaOH 31.00
Total 447.00 Total 447.00
Page 57 of 177
16. Nebivolol hydrochloride
Process Description:
Benzopyran-2-Carboxaldehyde Derivative treated with Trimethylsulfoxonium iodide In
presence of Potassium hydroxide & Water. The mass is further treated with Benzyl amine &
Toluene, Ammonium formate using Pd/Catalyst. The mass is crystallized from Methanol,
filtered & dried to give Nebivolol.
Route of Synthesis:
Page 58 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) Benzopyran-2- CarboxaldehydeDerivative 140.00 Stage-1 81.00
Trimethylsulfoxonium iodide 115.00 Aqu. Effluent 430.00
Potassium hydroxide 56.00
Water 200.00
Total 511.00 Total 511.00
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Stage-1 81.00 Stage-2 121.00 Benzyl amine 40.00 Toluene Rec 270.00 Toluene 300.00 Solvent Loss 30.00 Total 421.00 Total 421.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs)Stage-2 121.00 Stage-3 168.00 Ammonium formate 60.00 Methanol Rec 108.00 Hydrogen gas 1.00 Solvent Loss 12.00 Methanol 120.00 Hydrogen gas 1.00
Process loss 13.00 Total 302.00 Total 302.00
Stage-IV
Input QTY.(kgs) Output QTY.(kgs)Stage-3 168.00 Nevivolol 100.00 Methanol 400.00 Methanol Rec 360.00
Solvent Loss 40.00
Dry loss 28.00
Carbon dioxide 40.00 Total 568.00 Total 568.00
Page 59 of 177
17. Pantaprazol Sodium Process Description:
Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto
benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S
compound will react with sodium hypochlorite in presence of organic solvent to get PT-1
compound. PT-1 compound will reacts with sodium hydroxide in presence of organic solvent
to get Pantoprazole sodium sesquihydrate.
Route of Synthesis:
Page 60 of 177
Material Balance:
Stage-1
Input QTY.(KGS) Output QTY.(kgs)
Pantoprazole chloro compound 77 Stage-1 115
Diflouro Methoxy-2-MB 73.5 IPA MLs 627
NaOH 30 Evaporation loss 15.1
R.O. water 200.50 Evaporation loss 8.4
IPA 462 Aq. layer 77.5
Total 843 Total 843
Stage-2
Input QTY.(KGS) Output QTY.(kgs)
Stage-1 115 Stage-2 103.5
10% NaOCl 279 Evaporation loss 8
IPA 692 IPA MLs 885
R.O. water 186.5 Evaporation loss 4
Aq. layer 272
Total 1272.5 Total 1272.5
Stage-3
Input QTY.(KGS) Output QTY.(kgs)
Stage-2 103.5 Pantoprazole Sodium- API 100
NaOH 11 Evaporation loss 10
Acetone 623 Evaporation loss 7
R.O. water 18 Acetone MLs 638.5
Total 755.5 Total 755.5
Page 61 of 177
18. 5-(Difluoromethoxy)-2- {[( 3,4Dimethoxypyridin - 2-yl) methyl]thio}-1H-
benzimidazole
Process Description:
Pantoprazole chloro compound will react with 5-difluoromethoxy-2-mercapto
benzamidazole in presence of Base in organic solvent to get PT-S compound. PT-S.
Route of Synthesis:
Material Balance:
Stage-1
Input QTY.(KGS) Output QTY.(kgs)
Pantoprazole chloro compound 77 Stage-1 115
Diflouro Methoxy-2-MB 73.5 IPA MLs 627
NaOH 30 Evaporation loss 15.1
R.O. water 291.50 Evaporation loss 8.4
IPA 462 Aq. layer 168.5
Total 934 Total 934
Page 62 of 177
19. N-((4-Chloromethyl)-2-Thiozolyl) Guanidine Hydrochloride
Process Description:
Stage-1:
1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent
media to give Stage-2 as product.
Route of Synthesis:
Material Balance:
Stage-1
Input Qty. Output Qty
1,3-Dichloro acetone 53.00 Stage-1 88.97
Guanylthiourea 50.00 Acetone Rec. 161.00
Potassium Iodide 2.40 Generated water 7.51
Acetone 170.00 Inorganic solid waste 2.40
Organic solid waste 7.52
Solvent Loss 8.0
Total 275.40 Total 275.40
Page 63 of 177
20. Methyl 3-amino-2 butenoate
Process Description:
STAGE –1A:
Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6
hours. Filter the mass.
Route of Synthesis:
Material Balance:
Stage-1A
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146
Page 64 of 177
21. 2,4-Difluoro-2-(1h- 1,2,4-Triazole-1-Yl) Acetophenone (Dfta)
Process Description:
Stage-I:
Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to
below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride
into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and
hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC
completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor
and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material
and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt.
Route of Synthesis:
Material Balance:
Stage-I
Input QTY.(KGS) Output QTY.(KGS)
1,3-Difluorobenzene 200 Stage-I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chloride 210 AlCl3 gel for Rec. 1100 4-Amino-1,2,4-Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202
Hydrochloric acid 75
Ice & Water 1200 Total 4092 Total 4092
Page 65 of 177
22. cis-2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-
ylmethyl methane sulphonate
Process Description: Stage-I:
charge dimethyl formamide, cis-2[bromomethyl-2-(2,4 dichlorophenyl)1,3 dioxalane-4-
yl)methyl benzoate and 1H-1,2,4 triazole into a reactor. Charge sodium hydroxide solution
into the reactor.Heat to reflux and maintain for 8 hours. After completion of reaction, cool
the mass below 35°C and charge potassium carbonate. Stir the mass for 30 minutes and
filter. Charge the filtrate and distil off DMF completely. Charge water and toluene into the
reactor and stir for 30 minutes. Discard the bottom aqueous layer to ETP. Cool the organic
layer to 10-15°C. Centrifuge the material and wash with toluene. Dry the material at 60-65°C
to produce Cis-[2- (2,4-dichlorophenyl)-2-(1H,1,2,4-triazol-1yl methyl)1,3 dioxolan-
4yl]methanol.
Stage-II:
Charge methylene dichloride, Step-I compound and triethyl amine into a reactor. Slowly add
methane sulfonyl chloride into the reactor at 10-15°C. After completion of the reaction,
charge water and stir for 30 minutes. Separate the layers. Charge organic layer in to the
reactor and charge carbon. Stir for 30 minutes and filter the mass into another reactor. Add
hydrochloric acid into the reactor at 25-30°C. Cool the mass to 10-15°C. Centrifuge and wash
with methylene dichloride. Dry the material at 45-50°C to produce Cis-[2-(2, 4 -
dichlorophenyl) - 2 - (1H,1, 2, 4 - triazol - 1yl- methyl) 1,3-dioxolan-4yl]-methyl methane
sulfonate (ITR-INT-A).
Route of Synthesis:
Page 66 of 177
Mass Balance:
Stage-01 Int-A
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Cis-Bromobenzoate 111.3 Triazole derivative 95.8
1H,1,2,4-Triazole 70.4 Solvent rec (DMF) 181.7
Potassium carbonate 105.7 Solvent rec (Tol) 153.3
Dimethyl formamide 186.7 Aq. Effluent 238.3
Sodium hydroxide 10.6 Residue 64.5
Toluene 157.4 Solvent loss 9.1
Water 100.7
Total 742.7 Total 742.7
Stage-02 Int-A
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Triazole derivative 95.8 ITR-INT-A 101.5
Triethyl amine 40.2 Solvent rec (MDC) 187.0
Methane sulfonyl chloride 38.3 Aq. Effluent 92.0
Methylene chloride 193.8 Spent carbon 7.7
Activated Carbon 3.8 Residue 56.2
Sodium hydroxide 6.9 Solvent loss 6.8
Water 72.4
Total 451.2 Total 451.2
Page 67 of 177
23. 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine
Process Description:
Stage-I:
Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a
reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same
temperature. After completion of the reaction distil off dimethyl formamide completely.
Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30
min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge.
Wash the material in water. Slurry wash the cake with acetone to produce 1-(4-
Methoxyphenyl)-1-(4-nitrophenyl) piperazine.
Route of Synthesis:
Mass Balance:
Stage-01
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
1-(4-Methyxy) piperadine 86.9 Stage-I 132.4
Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9
Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2
Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1
Methanol 203.3 Aq. Effluent 176.5
Acetone 205.7 Spent carbon 3.5
Carbon 1.7 Residue 54.8
Water 130.3 Solvent loss 13.3
Total 877.7 Total 877.7
Page 68 of 177
24. 2-[[4-(2-Methoxyethyl)phenoxy]methyl-oxirane
Process Description:
Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol. After
completing reaction we will get the product.
Route of Synthesis:
Mass Balance:
STAGE-1 (Epoxide)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4MEP 100.00 Epoxide 126.00
Epichlorohydrine 100.00 Effluent 354.00
Caustic soda 30.00
Water 250.00
Total 480.00 Total 480.00
Page 69 of 177
25. 3''-acetyl-2''-hydroxy-4-(4 phenylbutoxy) benzanilide
Process Description:
Stage-1:
To a stirred solution of Dimethyl Formamide and Methylene dichloride is added 4-(4-
phenylbutoxy)benzoic acid. Charge drop wise thionyl chloride. After completion, distil out
Methylene Dichloride under vacuum. Cha
rge this reaction mass to stirred solution of 3-amino 2-hydroxy acetophenone in Methylene
dichloride and pyridine at 0-5°C. After completion of reaction, charge Hydrochloric acid and
separate layers. Wash with Sodium bicarbonate solution and evaporate organic layer to
yield N-(2-hydroxy-3- (3-oxo-3-(1H-tetrazol-5-yl) propanoyl)phenyl)- 4 - (4-phenylbutoxy)
benzamide.
Route of Synthesis:
Mass Balance:
Stage-1
Input QTY. (kgs) Output QTY. (kgs)
4-(4-phenylbutoxy)benzoic acid 100.00 Stage -1 125.00
1-(3-amino-2-hydroxyphenyl)
Ethanone
57.60 Methylene Dichloride(Reco) 570.00
Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00
Dimethyl Formamide 5.00 Effluent 519.30
Thionyl Chloride 59.00 Organic Residue 27.10
Pyridine 89.60 Process Emissions(SO2) 19.80
Hydrochloric acid 200.00
Sodium Bicarbonate 30.00
Water 150.00
Total 1279.20 Total 1279.20
Page 70 of 177
Group – II
26. Prasugrel Hydrochloride
Process Description:
Stage-I:
Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2-
c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for
4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the
filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload
the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material.
Stage-II:
Charge stage-I material,Methyl Ethyl Ketone, and acetic anhydride, heat the reaction mass
to reflux for 4 hrs. Cool the reaction mass to 5-10°C and filter spin, dry and unload the
material. Dry the material at 50-60°C for 2hrs. Cool the drier and unload the material
(Prasugrel).
Stage-III:
Charge Stage-II material, methanol andHCl and heat the reaction mass to reflux for 4 hrs.
Cool the reaction mass and filter, spin, dry and unload the material. Dry the material at 50-
60°C for 2 hrs. Cool the drier and unload the material (prasugrel crude).
Stage-IV:
Charge Stage-III material, Acetone and Methanol. Heat the reaction mass to reflux for 2 hrs.
Cool the reaction mass to 0-5°Cand filter, spin, dry and unload the material. Dry the material
at 50-60°C for 2 hrs cool the drier and unload the material.
Page 71 of 177
Route of Synthesis:
Page 72 of 177
Material Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 49 2-Bromo-1-cyclopropyl-2-(2-
flourophenyl)ethanone
44
Recovery Methanol 123
Loss of Methanol 9 5,6,7,7a-tetrahydrothieno[3,2-
c]pyridine-2-(4H)-one
27
Effluent 364.86
Potassium Hydroxide 11 Residue 8.14
Methanol 132
Purified water 340
Total 554 Total 554
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 49 Stage-II 50
Acetic anhydride 16 Recovery Methyl ethyl ketone 137
Methyl ethyl ketone 147 Loss of Methyl ethyl ketone 10
Residue 15
Total 212 Total 212
Page 73 of 177
Stage-III
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-II 50 Stage-III 52
Hydrogen Chloride 5 Recovery Methanol 142
Methanol 150 Loss of Methanol 8
Residue 3
Total 205 Total 205
Stage-IV
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-III 52 Prasugrel Hydrochloride 50
Acetone 156 Recovery Acetone 147.5
Methanol 156 Recovery Methanol 148
Loss of Acetone 8.5
Loss of Methanol 8
Residue 2
Total 364 Total 364
Page 74 of 177
27. 5-[2-Cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl] -5,6,7,7a-
tetrahydrothieno[3,2-c]pyridin-2(4H)-one
Process Description:
Stage-I:
Charge 2-Bromo-1-cyclopropyl-2-(2-flourophenyl)ethanone, 5,6,7,7a-tetrahydrothieno[3,2-
c]pyridine-2-(4H)-one, potassium hydroxide and MeOH. Heat the reaction mass to reflux for
4 hrs. Cool the reaction mass to RT. Filter the reaction mixture distil off solvent from the
filtrate and water to residue and cool it to 0-5°C. Filter the solid formed spin dry and unload
the material dry the material at 50-60°C for 2 hrs. Cool the drier and unload the material.
Route of Synthesis:
Material Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 49 2-Bromo-1-cyclopropyl-2-(2-
flourophenyl)ethanone
44
Recovery Methanol 123
Loss of Methanol 9 5,6,7,7a-tetrahydrothieno[3,2-
c]pyridine-2-(4H)-one
27
Effluent 364.86
Potassium Hydroxide 11 Residue 8.14
Methanol 132
Purified water 340
Total 554 Total 554
Page 75 of 177
28. Dabigatran
Process Description:
Stage-I:
The propanoic acid methyl ester derivate of formulae-I is dissolved in ethanol and acetic
acid hydrogenated with damp Pd/C at RT at 2 bar hydrogen pressure. After completion of
the reaction the catalyst is filtered off and dissolved in ethanol was added to filtrate. To get
formulae-II precipitated out which was filtered off and dried.
Stage-II:
The Tosylate salt obtained in the stage-I was dissolved in acetone and the mixture is
combined with hexyl chloroformate in presence of potassium hydroxide at temperature
15°C. After completion of the reaction the precipitated product is filtered off and washed
with acetone mixture. The resulting crude is crystallized with water.
Route of Synthesis:
Material Balance
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 42.3
Recovery Ethanol 1225
Loss of Methanol 25
Carbon dioxide 3.7
3-[(1-Methyl-2-{[4-(5-oxo-4,5-dihydro-
[1,2,4]oxadiazol-3-yl)-phenylamino]-
methyl)-1H benzoimidazole-
5carbonyl)-pyridin-2-ylamino]-
propionic acid ethyl ester
48.5
Residue 25
P-toluene sulphonic acid 12.5
Acetic acid 10
Ethanol 1250
Total 1321 Total 1321
Page 76 of 177
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 42.3 Dabigetran 50
Hexachlorofomate 14 Recovery Acetone 574.8
Acetone 600 Loss of Acetone 25.2
Potassium Hydroxide 4.8 Potassium chloride 6.3
Hydrochloric acid 0.19 Effluent 501.6
Purified water 500 Residue 3.3
Total 1161.2 Total 1161.2
Page 77 of 177
29. Famotidine
Process Description:
Stage-1:
1, 3-Dichloro acetone reacts with Guanylthiourea in the presence of Acetone as solvent
media to give Stage-2 as product.
Stage-2:
Stage-1 product reacts with Thiourea, N-Sulfamyl-3-chloropropionamidine, Sodium
hydroxide and acetic acid in the presence of Methanol as solvent media to give Stage-2 as
product.
Stage-3
Stage-2 product reacts with ammonia in the presence of Methanol as solvent media to give
Famotidine as product.
Chemical Reaction:
Page 78 of 177
Material Balance:
Stage-1
Input Qty. Output Qty
1,3-Dichloro acetone 53.00 Stage-1 88.97
Guanylthiourea 50.00 Acetone Rec. 161.00
Potassium Iodide 2.40 Generated water 7.51
Acetone 170.00 Inorganic solid waste 2.40
Organic solid waste 7.52
Solvent Loss 8.0
Total 275.40 Total 275.40
Stage-2
Input Qty. Output Qty
Stage-1 88.97 Stage-2 125.70
Thiourea 25.13 Methanol Rec. 3228.00
Sodium Hydroxide 40 Generated water 12.00
N-Sulfamyl-3-
chloropropionamidineHCl
74.00 Inorganic solid waste 70.60
Acetic acid 20.00 Organic solid waste 39.80
Methanol 3397.00 Solvent loss 169.00
Total 3645.10 Total 3645.10
Stage-3
Input Qty. Output Qty
Stage-2 125.70 Famotidine 100.00
Ammonia (23%) 24.00 Methanol Rec. 36.00
Acetic acid 5.00 Effluent Water 574.00
Activated Carbon 6.00 Spent Carbon 6.00
Water 525.00 Organic Residue 7.70
Solvent loss 1.00
Total 724.70 Total 724.70
Page 79 of 177
30. N-[(2'-Cyano[1,1'-biphenyl]-4-yl)methyl]-L valine methyl ester
Process Description:
Stage-1:
L-Valine reacts with Methanol in presence of Methanol as solvent media to give Stage-1 as
product.
Stage-2:
Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of
Methanol as solvent media to give Stage-2 as product.
Route of Synthesis:
Page 80 of 177
Mass Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage-1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Organic Residue 8.33
Solvent Loss 65.00
Process Loss 35.37 Total 1390.70 Total 1390.70
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Stage-1 50.00 Stage-2 90.00 4-Bromomethyl-biphenyl-2-carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00
Solvent Loss 30.00 Total 1277.00 Total 1277.00
Page 81 of 177
31. Amlodipinbesylate
Process Description:
Stage I:
Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the
mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the
mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom
aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with
toluene.
STAGE –1A: Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6 hours. Filter the mass.
STAGE –II:
Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0-
5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the
reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid
and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the
mass slowly to 10-15°C. Centrifuge the mass and wash with toluene.
STAGE –III:
Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add
orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for
4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into
the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain
for 4 hours at room temperature. After completion of the reaction, Charge water into the
reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely
under vacuum below 85°C. Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the material and wash with ethyl acetate.
Stage – IV:
Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the
reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the
material and wash with hexane.
Stage V:
Charge monomethyl amine and Stage IV material into a reactor and heat to 75-80°C. After
completion of the reaction, cool the mass to room temperature. Centrifuge the material to
produce Amlodipine Base compound.
STAGE –VI:
Charge methanol, Amlodipine Base compound into a reactor and add Benzene sulphonic
acid slowly for 3-4 hours at 45-50°C. After completion of reaction, distil off methanol
completely. Charge ethyl acetate into the reactor and cool to 0-5°C. Centrifuge the material
and wash with water followed by ethyl acetate. Dry the material at 50-55°C to give
Amlodipinbesylate.
Page 82 of 177
Route of Synthesis:
Page 83 of 177
Material Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage-I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 200 Solvent loss 6 Effluent 220 Total 541 Total 541
Stage-1A
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146
Page 84 of 177
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage-II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5
Sodium chloride 50
Sodium hydride 28
Toluene 215 Total 471 Total 471
Stage-III
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 147 Purified Water 130 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1413 Total 1413
Stage-IV
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-III 150 Stage IV 150 Stage-IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35
Solvent loss 14 Total 541 Total 541
Stage-V
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 175 Aq. Effluent 225 Total 325 Total 325
Stage-VI
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage V 100 Stage VI 100 Benzene Sulfonic acid 64 Sol. Rec(MeOH) 195 Methanol 200 Sol. Rec (EA) 243 Ethyl acetate 250 Aq. Effiuent 144 Purified water 100 Residue 20
Solvent loss 12 Total 714 Total 714
Page 85 of 177
32. Amlodipine base
Process Description:
Stage I:
Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the
mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the
mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom
aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with
toluene.
STAGE –1A:
Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6
hours. Filter the mass.
STAGE –II:
Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0-
5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the
reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid
and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the
mass slowly to 10-15°C. Centrifuge the mass and wash with toluene.
STAGE –III:
Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add
orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for
4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into
the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain
for 4 hours at room temperature. After completion of the reaction, Charge water into the
reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely
under vacuum below 85°C.
Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the
material and wash with ethyl acetate.
Stage – IV:
Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the
reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the
material and wash with hexane.
Stage V:
Charge monomethyl amine and Stage IV material into a reactor and heat to 75-80°C. After
completion of the reaction, cool the mass to room temperature. Centrifuge the material to
produce Amlodipine Base compound.
Page 86 of 177
Route of synthesis:
Page 87 of 177
Material Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage-I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 150 Solvent loss 6 Effluent 170 Total 491 Total 491
Stage-1A
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage-II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5
Sodium chloride 50
Sodium hydride 28
Toluene 215 Total 471 Total 471
Page 88 of 177
Stage-III
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effluent 167 Purified Water 150 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1383 Total 1383
Stage-IV
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-III 150 Stage IV 150 Stage-IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35
Solvent loss 14 Total 541 Total 541
Stage-V
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage IV 150 Stage V 100 MMA 275 Aq. Effluent 325 Total 425 Total 425
Page 89 of 177
33. 2,4-dihydro-4-[(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl]-2-(1-
methylpropyl)-3h-1,2,4-triazole-3-one
Process Description: Stage-I:
Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a
reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same
temperature. After completion of the reaction distil off dimethyl formamide completely.
Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30
min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge.
Wash the material in water. Slurry wash the cake with acetone to produce 1-(4-
Methoxyphenyl)-1-(4-nitrophenyl) piperazine.
Stage-II:
Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into
the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of
the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and
maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl)
piperazine.
Stage-III + IV:
Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine
compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours
at same temperature. After completion of the reaction, charge water into the reactor.
Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene
chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add
hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the
mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4-
methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide.
Stage-V:
Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add
formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass
and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H-
1,2,4-triazole-3-one.
Stage-VI:
Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to
reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2-
bromebutane completely. Charge DMF into the reactor and acidify the mass with
hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4-
[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one.
Stage-VII:
Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux.
After completion of the reaction, distil off HBr completely and charge water into the reactor.
Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce
2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-
triazole-3-one (ITR-INT-B).
Page 90 of 177
Route of Synthesis:
Page 91 of 177
Mass Balance:
Stage-01 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
1-(4-Methyxy) piperadine 86.9 Stage-I 132.4
Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9
Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2
Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1
Methanol 203.3 Aq. Effluent 176.5
Acetone 205.7 Spent carbon 3.5
Carbon 1.7 Residue 54.8
Water 130.3 Solvent loss 13.3
Total 877.7 Total 877.7
Page 92 of 177
Stage-02 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 132.4 Stage-II 118.3
Dimethyl formamide 238.4 Solvent Rec (DMF) 231.4
Palladium carbon 0.1 Gas loss 5.0
Hydrogen gas 10 Residue 19.2
Solvent loss 7.0
Total 380.9 Total 380.9
Stage-03-04 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-II 118.3 Stage-IV 136.0
Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0
Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2
Methylene chloride 246.0 Aq. Effluent 220.8
Hydragin hydrate 65.0 Residue 41.8
n-Butanol 147.8
Water 65.7 Solvent loss 8.6
Total 792.4 Total 792.4
Stage-05 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-IV 136.0 Stage-V 121.2
Formamidine acetate 63.6 Solvent Rec (DMF) 380.3
Dimethyl formamide 390.0 Residue 78.3
Solvent loss 9.7
Total 589.5 Total 589.5
Stage-06 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-V 121.2 Stage-VI 92.9
2-Bromo butane 125.2 Solvent Rec (DMF) 349.7
Potassium carbonate 51.0 Solvent Rec (2-BB) 92.0
Dimethyl formamide 357.1 Residue 148.8
Hydrochloric acid 38.4
Solvent loss 9.4
Total 692.8 Total 692.8
Stage-07 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-VI 92.9 ITR-INT-B 78.0
Hydrobromic acid 961.9 Hydrobromic acid rec 935.5
Soda ash 86.7 Aq. Effluent 217.6
Water 100.0 Solvent loss 10.4
Total 1241.5 Total 1241.5
Page 93 of 177
34. Metoprolol Tartrate
Process Description:
Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain
and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product
unload in HDPE Carboys.
Metoprolol Base take into Ethyl acetate and Methanol and a solution of Tartric acid in
Methanol at 60-65oC in 4 hours reflux and cooling. Product centrifuge and wash with Ethyl
Acetate. Finished product dry in FBD and packed in HDPE container.
Route of Synthesis:
Mass Balance:
Stage-I (Epoxide)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4MEP 100.00 Epoxide 126.00
Epichlorohydrine 100.00 Effluent 404.00
Caustic soda 30.00
Water 300.00
Total 530.00 Total 530.00
STAGE-2 (Metoprolol Base)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 126.00 Metoprolol Base 149.00
MIPA 300.00 Effluent 767.00
Water 400.00 Toluene Reco 260.00
Toluene 400.00 Solvent loss 140.00
HCL 60.00
Caustic lye 30.00
Total 1316.00 Total 1316.00
Page 94 of 177
STAGE-3 (Metoprolol Tartrate)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-2 100.00 Metoprolol Tartrate 118.00
Ehtyl Acetate 600.00 Ethyl acetate reco 540.00
Tartric Acid 25.00 Methanol reco 315.00
Methanol 350.00 Solvent loss 95.00
Dry loss 7.00
Total 1075.00 Total 1075.00
Page 95 of 177
35. 1-(Isopropylamino)-3-[4-(2-methoxyethyl) phenoxy]-2-propanol
Process Description:
Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain
and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product
unload in HDPE Carboy’s.
Route of Synthesis:
Mass Balance:
STAGE-1 (Epoxide)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4MEP 100.00 Epoxide 126.00
Epichlorohydrine 100.00 Effluent 404.00
Caustic soda 30.00
Water 300.00
Total 530.00 Total 530.00
STAGE-2 (Metoprolol Base)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 126.00 Metoprolol Base 149.00
MIPA 300.00 Effluent 718.00
Water 351.00 Toluene Reco 260.00
Toluene 400.00 Solvent loss 140.00
HCL 60.00
Caustic lye 30.00
Total 1267.00 Total 1267.00
Page 96 of 177
36. Metoprolol Succinate
Process Description:
Water take in Reactor add Epichlorohydrine and charge in 4.Methoxy Ethyl Phynol Maintain
and add Caustic soda solution reaction in 7 hours and water wash and distill it. Product
unload in HDPE Carboy’s.
Metoprolol Base take into Ethyl acetate and Methanol and a solution of Succinic acid in
Methanol at 60-65oC in 4 hours reflux and cooling. Product centrifuge and wash with
Ethyl Acetate. Finished product dry in FBD and packed in HDPE container.
Route of Synthesis:
Mass Balance:
STAGE-1 (Epoxide)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4MEP 100.00 Epoxide 126.00
Epichlorohydrine 100.00 Effluent 354.00
Caustic soda 30.00
Water 250.00
Total 480.00 Total 480.00
STAGE-2 (Metoprolol Base)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 126.00 Metoprolol Base 149.00
MIPA 300.00 Effluent 667.00
Water 300.00 Toluene Reco 260.00
Toluene 400.00 Solvent loss 140.00
HCL 60.00
Caustic lye 30.00
Total 1216.00 Total 1216.00
Page 97 of 177
STAGE-3 (Metoprolol Succinate)
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-2 100.00 Metoprolol Succinate 112.00
Ehtyl Acetate 400.00 Effluent 75.00
Succinic Acid 21.00 EA Reco 360.00
Methanol 70.00 Solvent loss 40.00
Dry loss 4.00
Total 591.00 Total 591.00
Page 98 of 177
37. Ketoconazole Process Description: Stage I:
CBB is reacted with IMD in the presence of DMF as solvent. The reaction mass is quenched in sodium bicarbonate solution and the product is extracted with toluene. The aqueous layer is kept for IMD recovery. The organic layer containing the product is reacted with sodium hydroxide solution. After completion of reaction, the pH of the mass is adjusted with hydrochloric acid. mass is diluted with water and centrifuged. The wet cake is dissolved in ethyl acetate and treated with carbon. The mass is filtered and the ethyl acetate is distilled off. The residue is cooled and centrifuged. The mass is dried to produce KT-I.
Stage II:
KT-I is reacted with PTSC in the presence of sodium carbonate and methylene chloride as
solvent. The reaction mass is diluted and the organic layer separated. Methylene chloride is
distilled off completely from the organic layer and the residue is diluted with methanol and
water. The mass is centrifuges and washed with methanol and water mixture. The mass is
dried to produce Cis-Tosylate (KT-II).
Stage-III:
Cis-Tosylate (KT-II) is reacted with Para hydroxyl phenyl N-acetyl piperazine and sodium
methoxide in the presence of dimethyl sulfoxide as solvent. After completion of the
reaction, sodium hydroxide solution is charged into the reactor and maintained. The mass is
centrifuged. The wet cake is treated with water and further by acetone. The wet cake is
taken for next stage.
Stage IV:
The wet cake is dissolved in ethyl acetate and methanol, and treated with carbon. The mass
is filtered and the solution distilled off. The residue is cooled and centrifuged. The material is
dried to produce Ketoconazole.
Route of Synthesis:
Page 99 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs)
CBB 780 Stage-1 450
IMD 693.3 IMD Rec 360
DMF 37.2 Toluene Rec 2207.0
Toluene 2275.5 Ethyle Acetate 1620.0
Sodium Bicarbonate 148.2 Aq. Effluent 1599.4
Sodium hydroxide 120.0 Spent carbon 12.0
Water 705.0 Residue 130.0
HCl 156 Process loss 254.9
Ethyl Acetate 1706.4
Activated Carbon 6.0
Vacuum Salt 6.0
Total 6633.3 Total 6633.3
Page 100 of 177
Stage-II
Input QTY.(kgs) Output QTY.(kgs)
Stage-1 450.0 Stage-2 600.0
Methylenechloride 3217.5 Methylenechloride Rec 3024.0
P-Toluene Sulfonyl Chloride 465.0 Methanol Rec 1375.0
Sodium Carbonate 307.5 Aq. Effluent 778.0
HCl 12.0 Process Loss 400
Methanol 1425.0
Water 420
Total 6297.0 Total 6297.0
Stage-III
Input QTY.(kgs) Output QTY.(kgs)
Stage-2 600 Stage-3 650.0
PeraHydroxy phenyl n-acetyl piperazine 285.0 Dimethyl Solfoxide Rec 779.0
Dimethyl Solfoxide 847.0 Acetone Rec 300.0
Sodium methoxide powder 70.0 Aq. Effluent 408.0
Sodium Hydroxide 50.0 Residue 59.0
Acetone 240.0 Process loss 68.0
Methnol 7.0
Water 165.0
Total 2264.0 Total 2264.0
Stage-IV
Input QTY.(kgs) Output QTY.(kgs)
Stage-3 650 Ketoconazole 510.0
Ethyl Acetate 2220.0 EA + Methanol Rec 2550.0
Methanol 464.0 Spent Carbon 40
Activated Carbon 20 Residue 80.0
Proess Loss 174.0
Total 3354.0 Total 3354.0
Page 101 of 177
38. Phthaloyl amlodipine
Process Description:
Stage I:
Charge toluene, phthalic anhydride and mono-ethanol amine into the reactor. Heat the
mass to reflux. Maintain for 4 hours at reflux. After completion of the reaction, cool the
mass below 35°C and charge water. Stir the mass and settle for 1 hour. Discard bottom
aqueous layer to ETP. Cool the mass to 10-15°C. Centrifuge the material and wash with
toluene.
STAGE –1A:
Charge Methyl acetoacetate and ammonia solution into the reactor and maintain for 6
hours. Filter the mass.
STAGE –II:
Charge toluene, sodium hydride and Stage I compound into the reactor. Cool the mass to 0-
5°C. Add ethyl 4-chloro acetoacetate into the reactor maintaining the temperature of the
reaction mass at 0-5°C. After completion of the reaction, charge diluted hydrochloric acid
and sodium chloride. Filter the mass and distil off toluene about 50% of volume and cool the
mass slowly to 10-15°C. Centrifuge the mass and wash with toluene.
STAGE –III:
Charge hexane and pyridine in the reactor, heat the reaction mass to 50°C. Add
orthochlorobenzaldehyde into the reactor for 4 to 5 hours at 50-55°C. Maintain the mass for
4 hours and distil off hexane completely below 55°C. Cool the mass and charge toluene into
the reactor followed by acetic acid. Charge stage-II compound into the reactor and maintain
for 4 hours at room temperature. After completion of the reaction, Charge water into the
reactor and stir. Discard the bottom aqueous layer to ETP. Distil off toluene completely
under vacuum below 85°C.
Cool the mass and charge ethyl acetate. Stir and cool the mass to 0-5°C. Centrifuge the
material and wash with ethyl acetate.
Stage – IV:
Charge hexane, Stage III compound and Stage-1A compound into the reactor. Heat the
reaction mass to reflux and maintain for 4 hours. Cool the mass to 25-30°C. Centrifuge the
material and wash with hexane.
Route of Synthesis:
Page 102 of 177
Page 103 of 177
Material Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Phthalic anhydride 100 Stage-I 100 Monoethanol amine 45 Solv Rec (Toluene) 190 Toluene 196 Residue 25 Purified Water 250 Solvent loss 6 Effluent 270 Total 591 Total 591
Stage-1A
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Methyl aceto acetate 40 Stage 1A 35 Liq ammonia 96 Aq. Effluent 111 Total 146 Total 146
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage I 100 Stage-II 125 Ethyl Chloroaceto acetate 55 Solv Rec (Toluene) 210 Hcl 5 Residue 131 Acetic acid 18 Solvent loss 5
Sodium chloride 50
Sodium hydride 28
Toluene 215 Total 471 Total 471
Stage-III
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Ortho Chlorobenzaldehyde 40 Stage III 150 Hexane 191 Sol. Rec (Tol) 488 Piperidine 2 Sol Rec.(EA) 343 Acetic acid 25 Sol Rec. (Hex) 183 Toluene 500 Aq. Effiuent 267 Purified Water 250 Residue 25 Stage II 125 Solvent loss 27 Ethyl acetate 350 Total 1483 Total 1483
Stage-IV
INPUT QTY.(KGS) OUTPUT QTY.(KGS) Stage-III 150 Stage IV 150 Stage-IA 35 Sol Rec (Hex) 342 Hexane 356 Residue 35
Solvent loss 14 Total 541 Total 541
Page 104 of 177
39. 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl] phenyl]-2-(1-
methylpropyl)-3H-1,2,4-triazol-3-one
Process Description: Stage-I:
Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a
reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same
temperature. After completion of the reaction distil off dimethyl formamide completely.
Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30
min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge.
Wash the material in water. Slurry wash the cake with acetone to produce 1-(4-
Methoxyphenyl)-1-(4-nitrophenyl) piperazine.
Stage-II:
Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into
the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of
the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and
maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl)
piperazine
Stage-III + IV:
Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine
compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours
at same temperature. After completion of the reaction, charge water into the reactor.
Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene
chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add
hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the
mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4-
methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide.
Stage-V:
Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add
formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass
and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H-
1,2,4-triazole-3-one
Stage-VI:
Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to
reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2-
bromebutane completely. Charge DMF into the reactor and acidify the mass with
hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4-
[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one.
Page 105 of 177
Route of Synthesis:
Page 106 of 177
Mass Balance:
Stage-01 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
1-(4-Methyxy) piperadine 86.9 Stage-I 132.4
Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9
Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2
Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1
Methanol 203.3 Aq. Effluent 176.5
Acetone 205.7 Spent carbon 3.5
Carbon 1.7 Residue 54.8
Water 130.3 Solvent loss 13.3
Total 877.7 Total 877.7
Stage-02 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 132.4 Stage-II 118.3
Dimethyl formamide 238.4 Solvent Rec (DMF) 231.4
Palladium carbon 0.1 Gas loss 5.0
Hydrogen gas 10 Residue 19.2
Solvent loss 7.0
Total 380.9 Total 380.9
Stage-03-04 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-II 118.3 Stage-IV 136.0
Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0
Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2
Methylene chloride 246.0 Aq. Effluent 350.8
Hydragin hydrate 65.0 Residue 41.8
n-Butanol 147.8
Water 195.7 Solvent loss 8.6
Total 922.4 Total 922.4
Page 107 of 177
Stage-05 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-IV 136.0 Stage-V 121.2
Formamidine acetate 63.6 Solvent Rec (DMF) 380.3
Dimethyl formamide 390.0 Residue 78.3
Solvent loss 9.7
Total 589.5 Total 589.5
Stage-06 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-V 121.2 Stage-VI 92.9
2-Bromo butane 125.2 Solvent Rec (DMF) 349.7
Potassium carbonate 51.0 Solvent Rec (2-BB) 92.0
Dimethyl formamide 357.1 Residue 148.8
Hydrochloric acid 38.4
Solvent loss 9.4
Total 692.8 Total 692.8
Page 108 of 177
GROUP – III
40. Montelukast Sodium
Process Description: Stage-I: 1-(Hydoxy methyl) cyclo propane Acetonitrile (MEC-4) is reacted with methane sulfonyl
chloride in presence of Diisoprpylethyl amine, and the product is further treated with Thiol
acetic acid to give MAN.
Stage-II: Condensation of MAN and (2-(2-(3(S)-(3-(2-(7-Chloro-2-quinolinyl) ethenyl) phenyl-3-
(methane sulfonyloxy) propyl)-2-propanol) (QUID-8) in the presence with n-butyl lithium in
the presence of toluene and Dimethyl foramide which on further hydrolysis with Caustic lye
to give MOK-1 –Nitrile
Stage-III: MOK-1 Nitrile underwent sodium hydroxide hydrolysis in the presence of toluene to give MOK-1. Stage-IV: MOK-1 treated with t-butyl amine protection with acetone acid to give MOK-2 butyl amine.
Stage- V: MOK-2 t-butylamine on further treatment with caustic flakes to give sodium Montelukast
(MOK-3). On further carbon purification with methanol to give Pure MK-3 salt (Montelukast
Sodium).
Route of Synthesis:
Page 109 of 177
Mass Balance:
Stage-I Input Qty.(KGS) Output Qty.(kgs)
N-vinyl pyrrolidone 108.1 Stage-I 96.5 Thiol acetic acid 74 Acetic acid 45.6 Diisopropyl ethylamine 6 Toluene recovered 1447.5 Toluene 1500 Toluene loss 7.5 Water 1000 Toluene residue 45 Methane sulfonyl Chloride 15 N-vinyl pyrrolidone 23.7
Thiol acetic acid 16.3
Diisopropyl ethylamine 6
Methane sulfonyl chloride 15
Water 1000 Total 2703.1 Total 2703.1
Stage-II Input QTY.(kgs) Output QTY.(kgs)
Stage-I 96.5 Stage-II 350.6
Thiophene-2-ethylamine 347.4 Water generated during reaction 11.1
Toluene 2000 Toluene recovered 1940 Water 600 Toluene loss 10 Acetic acid 10 Toluene residue 50 Sodium chloride 50 Stage-I 17.9 Carbon 5 Thiophene-2-ethylamine 64.3
Acetic acid 10
Carbon 5
Sodium chloride 50
Water 600 Total 3108.9 Total 3108.9
Page 110 of 177
Stage-III
Input QTY.(kgs) Output QTY.(kgs)
Stage-II 350.6
Stage-III (Crude Nateglinide Form
H) 235.6
Sodium hydroxide 24.7 Sodium methoxide 21.7 Methanol 1219.8 Ammonia 6.8 Toluene 1700 Methanol recovered 1152
Water 800 Methanol loss 6
Acetic acid 30 Methanol wastewater 12
Sodium chloride 70 Methanol residue 30
HCl for NaOH neutralization 7.9 Toluene recovered 1632
Toluene loss 6.8
Toluene residue 61.2
Stage-II 122.7
Methanol 6.9
Acetic acid 30
Sodium hydroxide 8.7
Sodium chloride 70
Water 784
NaCl from NaOH neutralization 12.7
Water from NaOH neutralization 3.9
Total 4203 Total 4203
Stage-IV
Input QTY.(kgs) Output QTY.(kgs)
Stage-III 235.6 Stage-IV 198.7
Tertiary butyl amine 29.4 Acetone recovered 1536
Acetone 1600 Acetone loss 7.2
Toluene 2000 Acetone residue 56.8
Carbon 5 Toluene recovered 1920
Toluene loss 10
Toluene residue 70
Stage-III 58.9
Tertiary butyl amine 7.4
Carbon 5 Total 3870 Total 3870
Page 111 of 177
Stage-V
Input QTY.(kgs) Output QTY.(kgs) Stage-IV 198.7 Montelukast Sodium 150 Sodium hydroxide 62.1 Tert-butylamine 18 Mdc 1800 Water generated during reaction 4.4 Acetic acid 25 MDC recovered 1737 Water 1000 MDC loss 9 Methanol 1000 MDC residue 54 Carbon 5 Methanol recovered 970 HCl for NaOH neutralization 47.6 Methanol loss 4
Methanol residue 26
Stage- IV 36.1
Acetic acid 25
Carbon 5
Sodium hydroxide 52.2
Water 947.9
NaCl from NaOH neutralization 76.3
Water from NaOH neutralization 23.5
Total 4138.4 Total 4138.4
Page 112 of 177
41. Valsartan
Process Description:
Stage-1:
L-Valine reacts with Methanol in presence of Methanol as solvent media to give Stage-1 as
product.
Stage-2:
Stage-1 product reacts with 4-Bromomethyl-biphenyl-2-carbonitrile in presence of
Methanol as solvent media to give Stage-2 as product.
Stage-3: Stage-2 product reacts with Valeryl chloride in presence of Methanol as solvent media to give Stage-3 as product.
Stage-4:
Stage-3 product reacts with Sodium azide; Tri butyl tin chloride undergoes
Hydrogenation in presence of Methanol as solvent media give Valsartan as product.
Route of Synthesis:
Page 113 of 177
Page 114 of 177
Mass Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs) L-Valine 45.00 Stage-1 50.00 Thionyl Chloride 45.70 Methanol Rec. 758.00 Methanol 800.00 Toluene Rec. 474.00 Toluene 500.00 Organic Residue 8.33
Solvent Loss 65.00
Process Loss 35.37 Total 1390.70 Total 1390.70
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Stage-1 50.00 Stage-2 90.00 4-Bromomethyl-biphenyl-2-carbonitrile 82.00 Toluene Rec. 565.00 Potassium carbonate 45.00 Effluent Water 569.78 Toluene 600.00 Organic Residue 9.22 Water 500.00 Process Loss 13.00
Solvent Loss 30.00 Total 1277.00 Total 1277.00
Stage-III
Input QTY.(kgs) Output QTY.(kgs) Stage-2 90.00 Stage-3 100.00 Valeryl Chloride 34.00 Toluene Rec. 660.00
Toluene 700.00 Effluent Water 444.80 TEA 20.00 Inorganic Solid Waste 10.00 Water 500.00 Organic Residue 16.93
Process Loss 12.27
Solvent Loss 35.00 Total 1279.00 Total 1279.00
Stage-IV
Input QTY.(kgs) Output QTY.(KGS) Stage-3 100.00 Valsartan 100.00 Sodium Azide 16.00 Toluene Rec. 660.00 Tri Butyl tin Chloride 80.00 MDC Rec. 475.00 Hydrogen Gas 0.50 Xylene Rec. 228.00 Sodium Hydroxide 20.00 N-Hexane Rec. 190.00 Xylene 240.00 Effluent Water 577.30 Toluene 700.00 Spent Carbon 10.00 Water 500.00 Organic Residue 9.22
Solvent Loss 82.00 Total 2406.50 Total 2406.50
Page 115 of 177
42. Venlafaxine Hydrochloride
Process Description:
Anisole reacts with Aluminium chloride and acetyl chloride in methylene chloride togive 4-
methoxy acetophene and 4-methoxy acetophenone reacts with dimethylformamide,
sodium acetate and sulfur to give thioacetamide reacts with Cyclohexanone in presence of
grignard reagent togive N,N Dimethyl-2-(1-hydroxy cycloridehexahydrate, in methanol to
give N,N Dimethyl-2-(4-methoxyphenyl)ethyl amine which reacts with Borohydride and
nickel chloride hexahydrate, in methanol to give N,N Dimethyl-2-
(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyineor(+/-) 1-(2- Dimethylamino)-1-(4-
methoxyphenyl)ethyl) cyclohexanol, which further crystallized in hydrochloride formation
inisopropanol HCL and ethyl acetate as solvent to give final product Venlafaxine
hydrochloride.
Route of Synthesis:
Page 116 of 177
Mass Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs)
4-Methoxy Benzoyl Cyanide 96.56 Stage-1 136.00
Methanol 349.52 Aqu Effluent 752.48
Sodium Methoxide 91.12 CFML 1957.04
Cyclohexanone 89.76 Toluene Reco 432.97
Toluene 481.08 Solvent Loss 48.11
Water 2228.08 Dry Loss 9.52
Total 3336.12 Total 3336.12
Page 117 of 177
Stage-II
Input QTY.(kgs) Output QTY.(kgs) Acetic Acid 815.00 Venafaxine Hydrochloride 100.00 Stage-1 136.00 Catalyst 5.00 Catalyst 5.00 Acetic Acid reco 773.00 Caustic soda 477.00 Reco loss 42.00 Formic soda 194.00 Aqu effluent 1457.00 Formaldehyde 112.00 Sodium sulphate 27.00 Hydrochloric acid 251.00 Hyflo 4.00
Ethyl acetate 2253.00 Carbon 1.00 Sodium Sulphate 27.00 Ethyl Acetate Reco 2139.00 Sodium chloride 34.00 Reco loss 114.00 Hyflo 4.00 IPML 1550.00 IPA 1460.00 Dry Loss 18.00
IPA HCL 109.00
Activated Charcoal 1.00
Water 352.00
Total 6230.00 Total 6230.00
Page 118 of 177
43. Levocetirizine Dihydrochloride
Process Description:
Stage-I:
1-[(4-Chlorophenyl) phenyl methyl]-4-[(phenyl sulphonyl] piperazine is deprotectedwith 4-
Hydroxy benzoic acid in Hydro bromic acid then is condensed with 2(2-
Chloroethoxyacetamide) in presence of Sodium carbonate in toluene and is reacted with
sodium hydroxide and Hydrochloric Acid in acetone to give Levocetrizine Di hydrochloride as
product.
Route of Synthesis:
Page 119 of 177
Mass Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
LevocetirizineDihydrochloride 50 1-[((4 Chlorophenyl)phenyl)methyl] -
4-[(phenylsulphonyl)]piperazine
46.20
Recovery Toluene 1440
2(2-Chloroethoxy )acetamide 14.90 Recovery MDC 1767
4-Hydroxy benzoic acid 16 Recovery Acetone 442
Hydrobromic acid 8.80 Loss of Toluene 75
Sodium hydroxide 8.70 Loss of MDC 93
Hydrochloric acid 15.80 Loss of Toluene 23
Sodium carbonate 11.50 Activated Carbon 4
Potassium iodide 1.70 Effluent 1000.24
Toluene 1515 Residue 41.36
MDC 1860
Acetone 465
Activated carbon 4
Purified water 968
Total 4935.60 Total 4935.60
Page 120 of 177
44. Pregabalin
Process Description:
Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge
R-(-)-3- (Carbamoylmethyl)-5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is
done at 0- 5°C then raise the temperature of the reaction mass up to 30-35°C. After reaction
monitoring, raise the temperature of the reaction mass to 55-60°C and apply carbon
treatment. The clear filtrate is then received in another reactor. Excess water is distilled off
from the reaction mass. The reaction mixture is acidified with concentrated Hydrochloric
acid. Reaction mass is then up to 80-85°C and after that gradual cooling to 25-30°C. The
material is centrifuged after maintaining of the reaction mass at 25-30°C for 4-6 hrs. The
dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to
reaction mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is
then centrifuged and dried in under vacuum.
Route of Synthesis:
Mass Balance:
Stage-1
Input QTY.(kgs) Output QTY.(kgs)
Sodium Hydroxide 347.2 Stage-1 162.5
4-CMH 250.00 Spent carbon and hyflo 28.00
Liquid Bromine 224.00 Spent ML 2623.7
Hyflo 12.50 Loss on drying 62.5
Activated carbon 3.00
Hydrochloric acid 450.00
Process water 1590.00
Total 2877.00 Total 2877.00
Stage-2
Input QTY.(kgs) Output QTY.(kgs)
Stage-1 215.00 Pregabalin 182.8
IPA 1290.00 Spent ML 1750.00
DM water 460.00 Loss on drying 32.2
Total 1965.00 Total 1965.00
Page 121 of 177
45. Veratric Acid
Process Description:
Stage -I:
Catechol is methylated by Dimethyl sulphate in presence of aqueous alkaline solution and
gives Veratrol (Veratric acid Stage-I) as an organic layer.
Stage II:
Veratric acid Stage-I (Veratrol) is acylated with Acetyl chloride in presence of anhydrous
aluminum chloride in Methylene dichloride solvent. Reaction mass is quenched in chilled
Hydrochloric acid solution to get Veratric acid Stage-II.
Stage III:
Veratric acid Stage-II (Acetyl Veratrol) is oxidized with Sodium hypochlorite and further it is
hydrolysed by Hydrochloric acid to give Veratric acid. Isolate solid by centrifugation and dry
it.
Route of Synthesis:
Page 122 of 177
Mass Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Catechol 350 Stage-I 400
Dimethyl Sulphate 875 Effluent 1782
Sodium hydroxide 288 Salt 6
Purified water 695 Guicol 20
Total 2208 Total 2208
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 400 Stage-II 445
Methylene dichloride 1680 Recovery Methylene Dichloride 1440
Aluminium chloride 500 Loss of Methylene Dichloride 240
Acetyl chloride 395 Poly Aluminium chloride 3300
Hydrochloric Acid 240
Sodium Bicarbonate 10
Purified water 2200
Total 5425 Total 5425
Stage-III
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-II 445 Veratric Acid 380
Methylene dichloride 500 Recovery Methylene Dichloride 440
Sodium Hypo Chlorite 4675 Loss of Methylene Dichloride 60
Activated Carbon 10 Residue 15
Hydrochloric Acid 1120 Effluent 6875
Sodium meta bi sulphate 30 Activated Carbon 10
Purified Water 1000
Total 7780 Total 7780
Page 123 of 177
46. Fluconazole
Process Description:
Stage-I:
Charge Methylene dichloride and aluminium chloride into the reactor. Cool the mass to
below 5°C. Charge 1,3-Difluorobenzene into the reactor. Add slowly chloroacetyl chloride
into the reactor for 4 to 5 hours below 10°C. Charge the reaction mass to ice and
hydrochloric acid. Stir the reaction mass for 4 hours and separate the layers. Distil off MDC
completely below 50°C. Charge isopropyl alcohol and 4-amino-1,2,4-triazole into the reactor
and maintain for 6 hours at 45-50°C. Cool the reaction mass to 10°C and centrifuge material
and dry to produce 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone salt.
Stage-II:
Charge water, sodium nitrite and 2-(1H-1,2,4-triazole-1-yl)-2’,4’-difluoroacetophenone into
the reactor and heat to 50-60°C. Slowly add hydrochloric acid at 50-60°C and maintain for
12 hours. Cool the mass below 20°C and neutralize the reaction mass with ammonia
solution. Centrifuge the mass and wash with water. Dry the material to produce 1-(2,4-
difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone.
Stage-III:
Charge Toluene, 1-(2,4-difluorophenyl)- 2-(1H,1,2,4-Triazol-1-yl) ethanone, potassium
hydroxide, 1,2,4,-Triazole and Trimethylsulphoxinium iodide into the reactor. Heat to reflux
and maintain for 12 hours.Distil off Toluene completely. Cool the reaction mass and charge
water into the reactor. Charge toluene into the reactor and stir for 30 minutes. Settle the
mass for 30 minutes. Separate the layers. Discard the bottom aqueous layer. Cool the mass
to 10°C and centrifuge. Dry the material to produce Fluconazole crude. Charge water, crude
and ammonia solution into the reactor. Check complete dissolution and charge carbon. Stir
for 30 min and filter over hyflow bed. Charge toluene and citric acid. Neutralize the mass
with hydrochloric acid. Stir for30 minutes and settle for 30 minutes. Separate the layers and
discard aqueous layer. Cool the mass. Centrifuge the mass and wash with toluene. Dry the
material to produce Fluconazole pharma.
Route of Synthesis:
Page 124 of 177
Material Balance:
Stage-I
Input QTY.(KGS) Output QTY.(KGS)
1,3-Difluorobenzene 200 Stage-I Compound 480 Aluminium Chloride 240 Sol Rec(MDC) 1050 Methylene Chloride 1200 Sol Rec (IPA) 740 Chloroacetyl chloride 210 AlCl3 gel for Rec. 1100 4-Amino-1,2,4-Triazole 162 Aq. Effluent 490 IPA 790 Residue 30 Sodium bicarbonate 15 Solvent loss 202
Hydrochloric acid 75
Ice & Water 1200 Total 4092 Total 4092
Stage-II
Input QTY.(KGS) Output QTY.(KGS)
Stage-I Compound 480 Stage-II 370 Sodium Nitrite 118 Aq. Effluent 1778
Hydrochloric acid 250
Water 1100
Ammonia Solution 200 Total 2148 Total 2148
Stage-III
Input QTY.(KGS) Output QTY.(KGS)
Stage-II 370 Stage-III 370 TrimethylSulphoxoniumIodiade 330 Sol Rec (Toluene) 550 1,2,4-Triazole 165 Aq. Effluent 1170 Potassium Hydroxide 235 Residue 50 Toluene 600 Solvent loss 60 Water 500 Total 2200 Total 2200
Page 125 of 177
Stage-IV
Input QTY.(KGS) Output QTY.(KGS)
Stage-III 370 Fluconazole 250 Toluene 1500 Solvent Reco (Tol) 1428 Activated carbon 15 Aq. Effuient 1478 Citric Acid 15 Spent Carbon 30 Ammonia solution 640 Spent hyflow 24 Hydrochloric Acid 180 Residue 50 Hyflowsupercell 12 Solvent loss 72 Water 600 Total 3332 Total 3332
Page 126 of 177
47. Itraconazole
Process Description: Stage-I:
charge dimethyl formamide, cis-2[bromomethyl-2-(2,4 dichlorophenyl)1,3 dioxalane-4-
yl)methyl benzoate and 1H-1,2,4 triazole into a reactor. Charge sodium hydroxide solution
into the reactor.Heat to reflux and maintain for 8 hours. After completion of reaction, cool
the mass below 35°C and charge potassium carbonate. Stir the mass for 30 minutes and
filter. Charge the filtrate and distil off DMF completely. Charge water and toluene into the
reactor and stir for 30 minutes. Discard the bottom aqueous layer to ETP. Cool the organic
layer to 10-15°C. Centrifuge the material and wash with toluene. Dry the material at 60-65°C
to produce Cis-[2- (2,4-dichlorophenyl)-2-(1H,1,2,4-triazol-1yl methyl)1,3 dioxolan-
4yl]methanol.
Stage-II:
Charge methylene dichloride, Step-I compound and triethyl amine into a reactor. Slowly add
methane sulfonyl chloride into the reactor at 10-15°C. After completion of the reaction,
charge water and stir for 30 minutes. Separate the layers. Charge organic layer in to the
reactor and charge carbon. Stir for 30 minutes and filter the mass into another reactor. Add
hydrochloric acid into the reactor at 25-30°C. Cool the mass to 10-15°C. Centrifuge and wash
with methylene dichloride. Dry the material at 45-50°C to produce Cis-[2-(2, 4 -
dichlorophenyl) - 2 - (1H,1, 2, 4 - triazol - 1yl- methyl) 1,3-dioxolan-4yl]-methyl methane
sulfonate (ITR-INT-A). Process description–ITR-INT-B: Stage-I:
Charge dimethyl formamide, potassium carbonate and 1-(4-Methyxy) piperadine into a
reactor. Heat the mass to 60-65°C. Add paranitrochlorobenzene for 3-4 hours at same
temperature. After completion of the reaction distil off dimethyl formamide completely.
Cool the mass and charge methanol and carbon into the reaction. Maintain the mass for 30
min at 50-55°C and filter into another reactor. Cool the filtrate to 10-15°C and centrifuge.
Wash the material in water. Slurry wash the cake with acetone to produce 1-(4-
Methoxyphenyl)-1-(4-nitrophenyl) piperazine.
Stage-II:
Charge DMF, palladium carbon and 1-(4-Methoxyphenyl)-1-(4-nitrophenyl) piperazine into
the reactor. Heat the mass to 50-55°C. Pass hydrogen gas for 18 hours. After completion of
the reaction, cool the mass below 35°C and filter the mass. Cool the filtrate to 0-5°C and
maintain. Centrifuge the mass to produce 1-(4-Methoxyphenyl)-1-(4-aminophenyl)
piperazine.
Stage-III + IV:
Charge Methylene chloride and 1-(4-Methoxyphenyl)-1-(4-aminophenyl) piperazine
compound into a reactor. Heat the mass to 35-45°C. Add phenyl chloroformate for 5-6 hours
at same temperature. After completion of the reaction, charge water into the reactor.
Separate the layers. Discard aqueous layer and charge organic layer. Distill off Methylene
chloride completely and charge n-butanol into the reactor. Heat the mass to 55-60°C. Add
hydrazine hydrate into the reactor. Maintain for 4 hours at same temperature and cool the
mass. Centrifuge the mass and wash with n-butanol to produce 2,4-Dihydro-4-[(4-
Page 127 of 177
methoxyphenyl)-1-piperazinyl]phenyl hydrazine carboxamide.
Stage-V:
Charge DMF and carboxamide compound into the reactor and heat to 70-75°C. Add
formanidineacetate into the reactor slowly. After completion of the reaction, cool the mass
and centrifuge, to produce 2,4-Dihydro-4-[4-[(4-methoxyphenyl)-1-piperazinyl phenyl]-3H-
1,2,4-triazole-3-one
Stage-VI:
Charge 2-bromobutane, potassium carbonate and triazole compound into a reactor. Heat to
reflux and maintain for 8 hours. After completion of reaction filter the mass and distil off 2-
bromebutane completely. Charge DMF into the reactor and acidify the mass with
hydrochloric acid. Centrifuge the material and wash with DMF to produce 2,4-Dihydro-4-[4-
[(4- methoxyphenyl)-1-piperazinyl phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one
Stage-VII:
Charge hydrobromic acid and stage-VI compound into a reactor and heat the mass to reflux.
After completion of the reaction, distil off HBr completely and charge water into the reactor.
Neutralize the mass with soda ash. Centrifuge the mass and wash with water to produce
2,4- Dihydro-4-[4-[(4-hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-
triazole-3-one (ITR-INT-B)
ITRA-Stage-I/II/III:
Charge water, potassium hydroxide, Cis-(2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl-
methyl)-1,3-dioxalane-4-yl) methyl methane sulfonate and 2,4-Dihydro-4-[4-[(4-
hydroxyphenyl)-1-piperazinyl] phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one into the
reactor. Heat the mass to 80-85°C and maintain for 6 hrs. Cool the mass below 35°C and
centrifuge. Charge the cake and DMF into a reactor and maintain for 1 hour at room
temperature. Centrifuge the mass and wash with DMF to produce Itraconazole crude. The
crude is treated with toluene, methanoland ethyl acetate and carbon to produce
Itraconazole pure.
Route of Synthesis:
Page 128 of 177
Page 129 of 177
Page 130 of 177
Material Balance:
Stage-01 Int-A
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Cis-Bromobenzoate 111.3 Triazole derivative 95.8
1H,1,2,4-Triazole 70.4 Solvent rec (DMF) 181.7
Potassium carbonate 105.7 Solvent rec (Tol) 153.3
Dimethyl formamide 186.7 Aq. Effluent 324.3
Sodium hydroxide 10.6 Residue 64.5
Toluene 157.4 Solvent loss 9.1
Water 186.7
Total 828.7 Total 828.7
Stage-02 Int-A
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Triazole derivative 95.8 ITR-INT-A 101.5
Triethyl amine 40.2 Solvent rec (MDC) 187.0
Methane sulfonyl chloride 38.3
Methylene chloride 193.8 Aq. Effluent 192.0
Activated Carbon 3.8 Spent carbon 7.7
Sodium hydroxide 6.9 Residue 56.2
Water 172.4 Solvent loss 6.8
Total 551.2 Total 551.2
Page 131 of 177
Stage-01 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
1-(4-Methyxy) piperadine 86.9 Stage-I 132.4
Paranitrochlorobenzene 71.2 Solvent Rec (Methanol) 198.9
Potassium carbonate 77.1 Solvent Rec (Acetone) 200.2
Dimethyl formamide 101.5 Solvent Rec (DMF) 98.1
Methanol 203.3 Aq. Effluent 176.5
Acetone 205.7 Spent carbon 3.5
Carbon 1.7 Residue 54.8
Water 130.3 Solvent loss 13.3
Total 877.7 Total 877.7
Stage-02 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 132.4 Stage-II 118.3
Dimethyl formamide 238.4 Solvent Rec (DMF) 231.4
Palladium carbon 0.1 Gas loss 5.0
Hydrogen gas 10 Residue 19.2
Solvent loss 7.0
Total 380.9 Total 380.9
Stage-03-04 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-II 118.3 Stage-IV 136.0
Phenyl chloroformate 78.6 Solvent Rec (MDC) 240.0
Sodium bicarbonate 71.0 Solvent Rec (Butanol) 145.2
Methylene chloride 246.0 Aq. Effluent 450.8
Hydragin hydrate 65.0 Residue 41.8
n-Butanol 147.8
Water 295.7 Solvent loss 8.6
Total 1022.4 Total 1022.4
Stage-05 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-IV 136.0 Stage-V 121.2
Formamidine acetate 63.6 Solvent Rec (DMF) 380.3
Dimethyl formamide 390.0 Residue 78.3
Solvent loss 9.7
Total 589.5 Total 589.5
Stage-06 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-V 121.2 Stage-VI 92.9
2-Bromo butane 125.2 Solvent Rec (DMF) 349.7
Potassium carbonate 51.0 Solvent Rec (2-BB) 92.0
Dimethyl formamide 357.1 Residue 148.8
Page 132 of 177
Hydrochloric acid 38.4
Solvent loss 9.4
Total 692.8 Total 692.8
Stage-07 Int-B
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-VI 92.9 ITR-INT-B 78.0
Hydrobromic acid 961.9 Hydrobromic acid rec 935.5
Soda ash 86.7 Aq. Effluent 476.6
Water 359.0 Solvent loss 10.4
Total 692.8 Total 692.8
Stage-01 Intraconazole
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
ITR-INT-A 101.5 IT-I 125.0
ITR-INT-B 78.0 Solvent Rec (DMF) 578.0
Water 287.5 Aq. Effluent 380.5
N,N-Dimethyl formamide 590 Residue 13.5
Potessium Hydroxide 52 Solvent loss 12.0
Total 1109 Total 1109
Stage-02 Itraconazole
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
IT-I 125.0 Intraconazole 85.00
Toluene 165.0 Solvent Rec (Toluene) 160
Ethyle Acetate 432.0 Solvent Rec (EA) 420
Methanol 695.9 Solvent Rec (Methanol) 675
Carbon 2.3 Residue 34.1
HyflowSupercell 6.7 Spent Carbon 4.6
Spent Hyflow 10.3
Solvent Loss 37.9
Total 1426.9 Total 1426.9
Page 133 of 177
48. Cetirizine Dihydrochloride
Process Description:
Stage-I:
The 4-Chloro benzhydeylpiperazine react with 2-chloroethanol in presence of Triethylamine
in toluene solvent. After reaction completion toluene was distilled under reduced pressure
and added acetone and passed dry hydrogen chloride gas to isolate 4-Chloro
benzhydrylpiperazineethoxy hydrochloride.
Stage-II:
The 4-Chloro benzhydrylpiperazineethoxycompound react with Sodium monochloro acetate
in presence of Potassium hydroxide in Dimethylformamide. After completion of reaction by
adding water and adjust pH to 9.0 and extract with toluene. Again the aqueous layer is
adjusted to pH 4.0 using Hydrogen chloride and the product is extracted with Methylene
Dichloride. Distilled Methylene Dichloride, added acetone and passed dry Hydrogen chloride
gas to isolate Cetirizine Dihydrochloride.
Route of Synthesis:
Page 134 of 177
Mass Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4-Chloro benzhydeylpiperazine 230 Stage-I 240
Toluene 800 Recovery Toluene 752
2-Chloroethanol 115 Recovery Triethylamine 232
Triethylamine 250 Loss of Toluene 48
Sodium carbonate 100 Less of Triethylamine 18
Purified water 2300 Effluent 2448.25
Residue 25.32
Carbon dioxide 31.43
Total 3795 Total 3795
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 240 Stage-II 250
Sodium monochloro acetate 175 Recovery Toluene 1175
Potassium hydroxide 85 Recovery Methylene dichloride 690
Dimethylformamide 50 Recovery Acetone 697
Toluene 1250 Loss of Toluene 75
Methylene dichloride 750 Loss of Methylene dichloride 60
Acetone 750 Loss of Acetone 53
Hydrogen chloride 130 Effluent 2073.27
Activated carbon 38 Residue 85.13
Purified water 750 Hydrogen chloride gas 21.6
Activated carbon 38
Total 5218 Total 5218
Page 135 of 177
49. Rebeprazol Sodium
Process Description:
Stage-1:
2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N- Oxide
it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1.
Stage-2:
Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2
Compound
Stage-3:
Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and
Hydrochloric Acid to get Stage-3 Compound
Stage-4:
Stage-3 Compound is reacted with Thionyl Chloride in the presence of MDC Solvent media
to get Stage-4 compound
Stage-5:
Stage-4 Compound is reacted with 2-Mercapto Benzimidazole, Sodium hydroxide in the
presence of Toluene Solvent Media to get Stage-5 Compound
Stage-6:
Stage-5 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base
Stage-7:
Rabeprazole Base is reacted with Sodium hydroxide to get Rabeprazole Sodium
Route of Synthesis:
Page 136 of 177
Page 137 of 177
Page 138 of 177
Mass Balance:
STAGE-1
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
2,3 Lutidine 46.00 Stage-1 65.00
Acetic acid 46.00 Spent acid 140.00
Hydrogen peroxide 33.00 Effluent 400.80
Nitric acid 30.00 Organic Residue 7.20
Sulfuric acid 108.00
Water 350.00
Total 613.00 Total 613.00
STAGE-2
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 65.00 Stage-2 80.00
3-Methoxy-1 –propanol
Acetic anhydride
40.00 Toluene Reco 235.00
Sodium hydroxide 18.50 DMSO Reco 188.00
Toluene 250.00 Solvent loss 22.00
DMSO 200.00 Inorganic solid waste 29.70
Organic waste 11.80
Water generate 7.00
Total 573.50 Total 573.50
STAGE-3
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-2 80.00 Stage-3 90.00
Acetic anhydride 150.00 Toluene Reco 660.00
NaOH 20.00 Acetic anhydride Reco 107.00
HCL 20.00 Effluent 360.50
Toluene 700.00 Organic Residue 13.50
Water 300.00 Process loss 39.00
Total 1230.00 Total 1230.00
STAGE-4
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-3 90.00 Stage-4 80.00
Thionyl chloride 53.00 MDC Reco 710.00
Sodium sulphate 10.00 Solvent loss 37.00
Water 500.00 Organic waste 10.00
MDC 750.00 Organic Residue 16.30
Process loss 23.20
Total 1403.00 Total 1403.00
Page 139 of 177
STAGE-5
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-4 80.00 Stage-5 100.00
2-mercapto benzimidazole 53.00 Toluene Rec. 375.00
Sodium Hydroxide 15.00 Solvent Loss 20.00
Toluene 400.00 Effluent 329.70
Water 300.00 Organic Residue 23.30
Total 848.00 Total 848.00
STAGE-6
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-5 100.00 Stage-6 100.00
Sodium hypochlorite (8%) 327.00 MDC Rec. 570.00
MDC 600.00 Acetone Rec. 137.00
Acetone 150.00 Effluent 944.30
Sodium Hydro Sulphate 12.00 Organic Waste 7.70
MMA in Methanol 10.00 Solvent Loss 40.00
Water 600.00
Total 1799.00 Total 1799.00
STAGE-7
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-6 100.00 Rabeprazole Sodium 100.00
Sodium hydroxide 13.00 IPA Rec. 280.00
Isopropyl Alcohol 300.00 Solvent Loss 15.00
Activated Carbon 10.00 Generated Water 5.00
Spent Carbon 10.00
Organic Residue 13.00
Total 423.00 Total 423.00
Page 140 of 177
50. Pranlukast
Process Description:
Stage-1:
To a stirred solution of Dimethyl Formamide and Methylene dichloride is added 4-(4-
phenylbutoxy)benzoic acid. Charge drop wise thionyl chloride. After completion, distil out
Methylene Dichloride under vacuum. Charge this reaction mass to stirred solution of 3-
amino 2-hydroxy acetophenone in Methylene dichloride and pyridine at 0-5°C. After
completion of reaction, charge Hydrochloric acid and separate layers. Wash with Sodium
bicarbonate solution and evaporate organic layer to yield N-(2-hydroxy-3- (3-oxo-3-(1H-
tetrazol-5-yl) propanoyl)phenyl)- 4 - (4-phenylbutoxy) benzamide.
Stage-2:
N-(2-hydroxy- 3- (3-oxo- 3-(1H-tetrazol-5-yl) propanoyl) phenyl)-4-(4-phenylbutoxy)
benzamide and sulfuric acid were charged in reactor. Reaction mass was heated at 80° C for
2-3 hours. After completion, reaction mass was quenched in ice water to yield crude
product.
Stage-3:
Pranlukast (crude) and ethyl acetate were charged in reactor and refluxed for 1 hour. Upon
cooling at 10°C. Solid slurry was filtered to obtain pure product.
Route of Synthesis:
Page 141 of 177
Mass Balance:
Stage-1
Input QTY. (kgs) Output QTY. (kgs)
4-(4-phenylbutoxy)benzoic acid 100.00 Stage -1 125.00
1-(3-amino-2-hydroxyphenyl)
Ethanone
57.60 Methylene Dichloride(Reco) 570.00
Methylene Dichloride(F/R) 588.00 Solvent Loss 18.00
Dimethyl Formamide 5.00 Effluent 769.30
Thionyl Chloride 59.00 Organic Residue 27.10
Pyridine 89.60 Process Emissions(SO2) 19.80
Hydrochloric acid 300.00
Sodium Bicarbonate 30.00
Water 300.00
Total 1529.20 Total 1529.20
Stage-2
Input QTY. (kgs) Output QTY. (kgs)
Stage -1 125.00 Stage -2 106.30
Sulfuric Acid 500.00 Effluent 1562.00
Water 1062.00 Organic Residue 18.8
Total 1687.00 Total 1687.00
Stage-3
Input QTY. (kgs) Output QTY. (kgs)
Stage -2 106.30 Stage -3 106.30
Ethyl Acetate (F/R) 900.00 Ethyl Acetate 862.50
Effluent 15.00
Organic Residue 6.3
Total 1006.30 Total 1006.30
Page 142 of 177
51. Zonisamide
Process Description:
Stage-I:
4-Hydroxycoumarin was reacted with hydroxylamine HCl in presence of potassium acetate
anhydrous in methanol at desired temperature and appropriate condition. Methanol
distillation, basification, dichloromethane washing and later acidification afforded
Zonisamide Stage-I.
Stage-II:
Obtained solid was reacted with complex of chlorosulphonic acid and 1, 4-dioxane in
ethylene dichloride. Quenching and later water removal and later chlorination using
phosphorus oxychloride in toluene and animation using ammonia afforded Zonisamide
Stage-II.
Stage-III:
Purification of Zonisamide Stage-II using acetone, water and activated charcoal afforded
pure Zonisamide.
Route of Synthesis:
Page 143 of 177
Mass Balance:
STAGE-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Methanol 153.00 Stage-1 214.00
4Hydroxy Coumarin 195.30 Methanol Reco 137.7
Hydroxylamine hydrochloride 293.00 Methanol loss 15.3
Potassium acetate 413.00 Effluent 1338.30
Sodium hydroxide 20.00 Dry loss 30.00
Methylene Dichloride 490.00 Organic Residue 29.00
Hydrochloric Acid 100.00
Water 600.00
Total 1764.30 Total 1764.30
STAGE-2
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 214.00 Stage-2 171.00
Ethylene Dichloride 856.00 HCL gas 20.00
1,4 Dioxane 97.00 EDC Reco 770.4
CSA 120.00 Ammonia gas 130.00
Sodium Sulphate 78.00 Toluene reco 270.00
Toluene 300.00 Aq Effluent 1603.40
Phosphorus Oxychloride 20.00 Solvent loss 115.60
Water 1400.00 Dry loss 35.00
Ammonia Gas 130.00
Total 3215.00 Total 3215.00
Stage-3
Input QTY.(kgs) Output QTY.(kgs)
Zonisamide (Crude) 180.00 zonisamide 125.00
Ethyl Acetate 1445 Ml CF 1454.00
Activated Carbon 7.00 Carbon + Hyflow 25.00
Hyflowsupercell 7.00 Dry In Loss 35.00
Total 1639.00 Total 1639.00
Page 144 of 177
52. Telmisartan Process description:
Bibenzimidazole&bromomethyl ester is condensed in presence of sodium methoxide in DMF to give Telmi-I (Methyl–[[4-Methyl-4’6(1-methyl-1H benzimidazol-2-yl)-2-propyl-1Hbenzimidazole -1yl] methyl] biphenyl-2-carboxylate).Telmi-I is hydrolyzed using potassium hydroxide in methanol & water mixture to give Telmisartan. Route of Synthesis:
Page 145 of 177
Material Balance:
Stage-I
Input QTY.(kgs) Output QTY.(kgs)Bibenzimidazole 186.7 (Stage- I) - termi-I 261.4 Bromo methyl ester 187.3 Dimethyl formamide Rec 921.1 Sodium hydroxide 33.1 Acetone Rec 280.3 Dimethyl formamide 969.6 Methanol Rec 18.6
Acetone 295.1 Wastewater Water 1240.9 Water 1240.9
Sodium bromide 63
Organic waste
Dimethyl formamide 9.7
Acetone 3
Methanol 0.2
Organics 63.1
Process Loss 51.4 Total 1692.7 Total 1692.7
Stage-II
Input QTY.(kgs) Output QTY.(kgs)(Stage- I) - Termi-I 261.4 Telmisartan 222.2 Potassium hydroxide 76.1 Methanol Rec 3141.6 Acetic acid 470.6 Water 2660.1 Methanol 3304.6 Potassium acetate 133 Activated carbon 13.1 Spent carbon 21.9 Celite 8.8 Methanol 46.3 Water 2817 Water 170.8
Organics 33.8
Acetic acid 389.1
Process loss 132.8 Total 3810 Total 3810
Page 146 of 177
53. Rosuvastatin Calcium
Process Description:
Stage-1:
4-Fluoro-Benzadehyde reacts with 4-Methyl-3-oxo-pentanoic acid ethyl ester in presence of
Base to give Stage-1 as product.
Stage-2:
Stage-1product reacts with S-Methyl isothio urea and 2,3 Dichloro-5,6-dicyano benzo
quinine in presence of HMPA to give stage-2as product.
Stage-3:
Stage-2 product reacts with meta-chloro peroxy benzoic acid to give Stage-4 as product and
Meta chlorob enzoic acid as by-product.
Stage-4
Stage-3 product reacts with methyl amine in presence of Ethanol solvent media to give
Stage-4 as product.
Stage-5
Stage-4 product reacts with Methane sulfonyl chloride in presence of Sodium hydride as
catalyst to give Stage-5 as product.
Stage-6
Stage-5product under goes reduction and oxidation in presence of Hydrogen gas to give
Stage-6 as product.
Stage-7
Stage-6 product reacts with methyl (3R)-3-(tert-butyldimethyl silyloxy)-5-oxo-6- triphenyl
phosphoranyli denehexanoate.
Stage-8
Stage-7 product reacts with Hydrogen fluoride in presence of Aceto nitrile as solvent media
to give Stage-8 as product.
Stage-9
Stage-8 product reacts with Sodium Boro hydride under goes hydrogenation to give Stage-9
as product.
Stage-10
Stage-9 product reacts with Calcium chloride under goes saponification to give Rosuvastatin
Calcium as product.
Page 147 of 177
Route of Synthesis:
Page 148 of 177
Page 149 of 177
Page 150 of 177
Page 151 of 177
Page 152 of 177
Mass Balance:
STAGE-1
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4-Fluorobenzaldehyde 52.00 Stage-1 100.00
4-Methyl-3-oxo-pentanoic
acid ethyl ester
66.30 Methanol Recovery 237.00
Potassium hydroxide 23.50 Methanol Loss 12.00
Methyl Iodide 60.00 Effluent water 590.56
Methanol 250.00 Organic Residue 11.24
Water 500.00
Total 951.80 Total 951.80
STAGE-2
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-1 100.00 Stage-2 115.00
S-Methyl isothiourea 35.00 MDC Recovery 474.00
2,3-Dichloro-5,6-
dicyano benzoquinone
85.00 MDC Loss 25.00
HMPA 100.00 HMPA Recovery 94.50
MDC 500.00 HMPA Loss 5.00
Water 300.00 Effluent water 307.81
By-Product 85.75
Organic Residue 12.44
Total 1120.00 Total 1120.00
STAGE-3
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-2 115.00 Stage-3 120.00
Metachloroperoxybenzoicacid 118.68 MDC Recovery 284.50
MDC 300.00 MDC Loss 15.00
Water 500.00 Effluent water 500.50
Metachloro benzoic
acidReuse
107.67
Organic Residue 6.01
Total 1033.68 Total 1033.68
STAGE-4
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-3 120.00 Stage-4 96.00
Methyl amine 10.20 Ethanol Recovery 238.00
Ethanol 250.00 Ethanol Loss 12.00
Methanol 300.00 Methanol Recovery 284.50
Water 300.00 Methanol Loss 15.00
Effluent water 327.23
Organic Residue 7.47
Page 153 of 177
Total 980.20 Total 980.20
STAGE-5
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-4 96.00 Stage-5 112.00
Methanesulfonyl chloride 35.00 Di methoxyethane Recovery 285.00
Sodium hydride(60%) 1.00 Di methoxyethane Loss 15.00
Di methoxyethane 300.00 Hydrochloric acid reuse 11.15
Organic Residue 8.85
Total 432.00 Total 432.00
STAGE-6
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-5 112.00 Stage-6 95.00
Hydrogen 0.56 Toluene Recovery 284.00
DIBAL-H 1.00 Toluene Loss 15.00
Toluene 300.00 Ethanol Recovery 13.04
Organic Residue 6.52
Total 413.56 Total 413.56
STAGE-7
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-6 95.00 Stage-7 155.00
Methyl(3R)-3-(tert butyl di methyl
silyloxy)-5-oxo-6-
triphenylphosphoranylidenehexa
noate
144.55 N,N-Dimethyl formamide
Recovery
280.00
Triethylamine 15.00 N,N-Dimethyl formamideLoss 15.00
N,N-Dimethyl formamide 300.00 Effluent water 320.00
Water 300.00 Organic Residue 9.33
By-Product 75.22
Total 854.55 Total 854.55
STAGE-8
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-7 155.00 Stage-8 120.00
Hydrogenfluoride 5.10 THF Recovery 237.00
THF 250.00 THF Loss 12.00
Ethyl acetate 300.00 Ethyl acetate Recovery 285.00
Ethyl acetate Loss 15.00
By-Product 34.24
Organic Residue 6.86
Total 710.10 Total 710.10
Page 154 of 177
STAGE-9
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-8 120.00 Stage-9 115.00
Hydrogen 0.48 Ethyl acetate Recovery 237.50
Diethyl methoxyborane 20.00 Ethyl acetate Loss 12.00
Sodium borohydride 1.00 THF Recovery 474.50
Ethyl acetate 250.00 THF Loss 25.00
THF 500.00 Sodium Borohydride Residue 1.00
Organic Residue 26.48
Total 891.48 Total 891.48
STAGE-10
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-9 115.00 Rosuvastatin Calcium 100.00
Calciumchloride 13.00 Toluene Recovery 473.50
Toluene 500.00 Toluene Loss 25.00
Ethyl acetate 500.00 Ethyl acetate Recovery 475.00
Water 250.00 Ethyl acetate Loss 25.00
Effluent water 262.82
Organic Residue 16.68
Total 1378.00 Total 1378.00
Page 155 of 177
54. Posaconazole
Process Description:
Stage-I:
4-Hydroxyphenyl-piperazinyl triazolone is added to Sodium hydroxide solution mixture.
Then add (5R,Cis)-toluene-4-sulfonic acid-5-(2,4-difluorophenyl)-5-(1H-1,2,4-triazol-1-
yl)methyl tetrahydrofuran-3-yl methylester and Ethyl acetate, combine layers and wash with
Sodium chloride solution. Then centrifuge the mass to collect the Stage-I material.
Stage-II:
Add Stage-I material, Add Pd/C then add Hydrochloric acid to the reaction mass.
Hydrogenate the reaction mass adjust pH using Sodium Hydroxide. The wet material charge
again into the reactor and add Acetone. Then centrifuge the mass to collect Stage-II
(Posaconazole (crude)) material.
Stage-III:
Methylene Dichloride and Isopropyl Alcohol is used as a solvent. Filter the mass to remove
the particles. Add Isopropyl Alcohol to the mass and heat the mass. Then cool the reaction
mass and centrifuge the mass to collect the Posaconazole (Pure).
Route of Synthesis:
Page 156 of 177
Page 157 of 177
Mass Balance:
Stage-I
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
4-Hydroxyphenyl-piperazinyl triazolone 14 Stage - I 18
Recovery Ethyl Acetate 130.5
Recovery Dimethyl
Sulfoxide
103.5
Recovery Isopropyl Alcohol 454.5
(5R,Cis)-toluene-4-sulfonic acid-5-(2,4-
difluorophenyl)-5-(1H-1,2,4-triazol-1-
yl)methyl tetrahydrofuran-3-yl
methylester
14
Loss of Ethyl Acetate 9.5
Sodium Hydroxide 2 Loss of Dimethyl Sulfoxide 6.5
Hydrochloric Acid (35%) 2 Loss of Isopropyl Alcohol 25.5
Sodium Chloride 14 Effluent 320.19
Ethyl Acetate 140 Residue 7.81
Dimethyl Sulfoxide 110
Isopropyl Alcohol 480
Purified Water 300
Total 1076 Total 1076
Stage-II
INPUT QTY.(KGS) OUTPUT QTY.(KGS)
Stage-I 18 Stage – II 11
Hydrogen 0.5 Recovery Methanol 216
Hydrochloric Acid (35%) 6 Recovery Acetone 117
Sodium Hydroxide 7 Recovery Isopropyl Alcohol 150.5
Methanol 230 Loss of Methanol 14
Acetone 190 Loss of Acetone 73
Isopropyl Alcohol 160 Loss of Isopropyl Alcohol 9.5
Palladium Carbon 9 Effluent 731
Purified Water 720 Residue 9.05
Palladium Carbon 9
Process Emission 0.45
Total 1340.5 Total 1340.5
Page 158 of 177
55. Ursodiol
Process Description:
Stage-1: Preparation of Ketolithocholic acid.
KSM (Chenodeoxycholic acid) oxidized using N-Bromosuccinamide in Acetone Water as
solvent atroom temperature to get 7-Ketolithocholic acid crude which is further purified in
Ethyl acetate,methanol, and water to get pure 7-Ketolithocholic acid (Stage-1).
Stage-2: Preparation of Ursodiol Crude
7-Ketolithocholic acid (Stage-1) reduced in presence of Metal Alloy (Ra/ni) in presence of
BasePotassiumtert. Butoxide in IPA to get Ursodiolcrude.
Stage-3: Preparation of UrsodiolTriethyl amine Salt.
Ursodiolcrude, which is salting with Triethyl amine in Acetone, water to get URSO TEA salt.
This TEA salt is desalting with 10% HCl solution to get Ursodiol.
Route of Synthesis:
Page 159 of 177
Mass Balance:
Page 160 of 177
ANNEXURE - IV
___________________________________________________________________________
DETAILS OF WATER CONSUMPTION AND WASTEWATER GENERATION
WATER CONSUMPTION & WASTEWATER GENERATION:
• Domestic wastewater (1.2 KL/day) will be treated and disposed in septic tank & soak
pit.
• Low COD & TDS Industrial wastewater (5 KL/day) will be treated in primary ETP and
sent to CETP of M/s. PETL for further treatment & disposal.
• High COD & TDS Industrial wastewater (0.33 KL/day) will be sent to Common Spray
Dryer of M/s. PETL for further treatment & disposal.
Proposed Scenario (KL/Day) Sr.
No.
Category
Water
Consumption
(KL/Day)
Wastewater
Generation
(KL/Day)
1. Industrial
Process 7.0 4.33
Boiler 1.5 0.2
Cooling 1.4 0.2
Washing 0.6 0.6
Total (Industrial) 10.5 5.33
2. Gardening 1.0 NIL
3. Domestic 1.5 1.2
Total 13.0 6.53
Page 161 of 177
Water Balance Diagram:
4 KL/Day
0.33 KL/Day
(High COD Stream)
Water: 13.0 KL/Day
Domestic:
1.5 KL/Day
Industrial:
10.5 KL/Day
Gardening:
1.0 KL/Day
Process:
4.33 KL/Day
Boiler:
1.5 KL/Day
Cooling:
1.4 KL/Day
Washing:
0.6 KL/Day Process:
7.0 KL/Day
ETP: 5 KL/Day
Cooling:
0.2 KL/Day
Washing:
0.6 KL/Day
Septic Tank /
Soak pit:
1.2 KL/Day
Boiler:
0.2 KL/Day
CETP
(M/s. PETL)
Common Spray
Dryer (M/s. PETL)
Page 162 of 177
ANNEXURE - V
___________________________________________________________________________
DETAILS OF EFFLUENT TREATMENT PLANT (ETP)
PROCESS DESCRIPTION OF EFFLUENT TREATMENT PLANT:
First all non-toxic and biodegradable streams of wastewater shall be collected in
Equalization cum Neutralization Tank (ENT-01) where the continuous addition and stirring of
Lime solution is done to maintain neutral pH of wastewater from Lime Dosing Tank (LDT-01)
as per requirement by gravity. Pipe grid is provided at bottom of the ENT-01 to keep all
suspended solids in suspension and to provide proper mixing by air supplied through air
blowers (B-01).
Then after, neutralized wastewater shall be pumped to Flash Mixer (FM-01). Alum and
Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and Polyelectrolyte Dosing
Tank (PEDT-1) respectively by gravity into FM-01 to carry out coagulation by using a Flash
Mixer. Then after, coagulated wastewater shall be settled in Primary Settling tank (PST-01).
Clear supernatant from PST-01 shall be collected in Intermediate Sump (IS-01).
Treated effluent from IS-01 then passed through Dual Media Filter (DMF-01) to remove
remaining SS from effluent. Then clear Water shall be collected in treated effluent Sump
(TES-01) before sent to common effluent treatment plant for further treatment & disposal.
Sludge settled in PST-01 shall be sent to Sludge Drying Beds (SDBs-A/B) where, dewatering
shall be carried out before storage in HWSA and ultimate disposal to TSDF. Leachate from
SDBs-A/B shall be pumped back to ENT-01 for further treatment.
Page 163 of 177
SIZE OF TANKS
S.N. Name of unit Size (m x m x m) No. MOC/ Remark
Flow = 5 KLD
1 Equalization cum Neutralization
Tank (ENT-01) 1.6 x 1.6 x 2.0 1 RCC M25
2 Flash Mixer (FM-01) 0.8x 0.8 x 1.5 LD 1 MSFRP
3 Primary Settling Tank(PST-01) 1.5 x 1.0 x 1.2 1 MSFRP
4 Intermediate Sump (IS-01) 1.5 x 1.0 x 1.2 1 MSFRP
5 Dual Media Filter (DMF-01) 300 lit/hr 1 FRP
6 Treated Effluent Sump (TES-01) 2.5 x 2.0 x 2.0 1 RCC M25
7 Lime Dosing Tank (LDT-01) 250 lit 1 HDPE
8 Alum Dosing Tank (ADT-01) 250 lit 1 HDPE
9 Poly Dosing Tank (PDT-01) 100 lit 1 HDPE
10 Sludge Drying Beds (SDBs-A/B) 2.0 x 3.0 2
Bk. Mas. With
PCC Bedding+
filling Media
RCC M25 = REINFORCED CEMENT CONCRETE (M 25 GRADE)
PCC = PLAIN CEMENT CONCRETE
HDPE = HIGH DENSITY POLY ETHELINE
BK.MAS. = BRICK MASONARY
EXPECTED CHARACTERISTICS OF WASTEWATER BEFORE & AFTER TREATMENT
Characteristics (mg/L) Sr.
No.
Parameter
Untreated Treated
CETP Inlet Norms
(mg/L)
1. pH 3-9 6.5-8.5 6.5-8.5
2. SS 150 70 100
3. COD 3000 2500 3000
4. BOD3 1000 800 1200
Page 164 of 177
Flow Diagram of Effluent Treatment Plant:
Page 165 of 177
ANNEXURE - VI
___________________________________________________________________________
DETAILS OF AIR POLLUTION CONTROL SYSTEM
Flue Gas Emission:
The flue gas emission through stack attached to IBR Boiler, Thermo pack & DG Set shall
conform to the following standards:
Sr.
No.
Process stack
attached to
Height from
ground level
Consumption
of fuel
Air pollution
control system
Expected
Pollutants
1 IBR boiler
(2 TPH)
11 meter Natural Gas =
300 SM3/Day
Adequate Stack
height will be
provided.
2 Thermo pack
(2 Lakhs
Kcal/hr.)
13 meter Natural Gas =
200 SM3/Day
Adequate Stack
height will be
provided.
3 DG Set
(100 KVA)
11 meter Diesel =
50 Liter/Day
Adequate Stack
height will be
provided.
PM = 150 mg/Nm3
SO2 = 100 ppm
NOx = 50 ppm
Process Gas Emission:
The details of process gas emission from reaction vessel are as below:
Sr.
No.
Process stack
attached to
Height from
ground level
Consumption
of fuel
Air pollution
control system
Expected
Pollutants
1 Reaction
Vessel
11 meter -- Two Stage
Scrubber
Cl2 = 9 mg/Nm3
HCl = 20 mg/Nm3
Page 166 of 177
ANNEXURE - VII
___________________________________________________________________________
DETAILS OF HAZARDOUS WASTE GENERATION, STORAGE & DISPOSAL
Sr.
No.
Type of waste Category Quantity
Disposal Method
1 ETP Sludge 35.1 5
MT/Month
Collection, Storage, Transportation
& Disposal to TSDF site (M/s. BEIL or
M/s. PSWML)
2 Discarded Bags/
Drums/ Carboys
33.1 800
Nos./Month
Collection, Storage, Transportation,
Decontamination and sell to GPCB
authorized vendors
3 Process Residue -- 5
MT/Month
Collection, Storage, Transportation
& sent to cement industries for co-
processing or sent to CHWIF for
incineration.
4 Used oil 5.1 0.075
KL/Month
Collection, Storage, transportation
and disposal by sell to registered
reprocessor
Page 167 of 177
ANNEXURE - VIII
___________________________________________________________________________
DETAILS OF HAZARDOUS CHEMICALS STORAGE & HANDLING
Sr.
No.
Name of the
Material
Type of
Hazard
Kind of
storage
Max. Qty.
to be stored
(MT)
Storage condition
i.e. Temp., Pressure
1 Acetic Acid Corrosive Drums 4745.50 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
2 Acetic Anhydride
Flammable
Drums
471.00
Keep container in a cool, well-
ventilated area. Keep container
tightly closed
3 Acetone Corrosive Drums 115385.50 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
4 Activated carbon Flammable Store in
Bag/
Drums
365.55 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
5 Aluminium
Chloride
Corrosive Store in
Bag/
Drums
2136.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area.
6 Ammonia Gas Corrosive Cylinder 520.00 Store in a cool and well
ventilated place
7 Ammonia
Solution
Corrosive Drums 1680.00 Store in a cool and well
ventilated place
8 Sodium Sulphate Corrosive Store in
Bag/
Drums
412.50 Keep container tightly closed.
Keep container in a cool, well-
ventilated area. Hygroscopic
9 Aniline Toxic Drums 170.00 Store in light-resistance
container. Keep container in a
cool, well-ventilated area. Keep
container tightly closed
10 Benzene Sulfonic
Acid
Corrosive Drums 320.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area.
11 Bromine Corrosive Glass
bottle
1298.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area.
12 Butanol Flammable Drums 515.00 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
13 Chloro Acetyl
Chloride
Flammable Drums 710.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area
Page 168 of 177
14 Caustic lye Corrosive Store in
Bag/
Drums
366.50 Keep container tightly closed.
Keep container in a cool, well-
ventilated area. Hygroscopic
15 Citric acid Corrosive Store in
Bag/
Drums
30.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area
16 Hydrochloric Acid Corrosive Drums 17169.85 Keep container tightly closed.
Keep container in a cool, well-
ventilated area.
17 Di Methyl
Formamide
Flammable Drums 8935.00 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
18 Pyridine Corrosive Drums 1792.00 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
19 Formaldehyde Flammable Drums 351.40 Store away from sources of
heat or ignition, strong alkalis,
acids, combustibles and
oxidizing agents.
20 Hydrogen gas Flammable Cylinder 78.50 Keep away from heat. Keep
away from sources of ignition.
Keep container tightly closed.
Keep in a cool, well-ventilated
place
21 Iso Propyl
Alcohol
Flammable Drums 62347.00 Keep container in a cool, well-
ventilated area. Keep container
tightly closed
22 Liq Ammonia Corrosive Cylinder 705.00 Store in a cool, well-ventilated
place. Store and use with
adequate ventilation.
23 Liq. Bromine Flammable Store in
Bag/
Drums
1298.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area
24 Methanol Flammable Drums 31851.7 Keep away from heat. Keep
away from sources of ignition.
Keep container tightly closed.
Keep in a cool, well-ventilated
place
25 Nitric acid Corrosive Drums 75.00 Keep container in a cool, well-
ventilated area. Separate from
acids, alkalies, reducing agents
and combustibles.
26 Sodium Nitrite Corrosive Store in
Bag/
Drums
575.00 Keep container in a cool, well-
ventilated area. Separate from
acids, alkalies, reducing agents
27 Succinic Acid Corrosive Store in
Bag/
133.00 Keep container tightly closed.
Keep in a cool, well-ventilated
Page 169 of 177
Drums place
28 Sulfuric acid Corrosive Drums 10270.00 Keep container tightly closed.
Keep in a cool, well-ventilated
place
29 Tartric Acid Corrosive Store in
Bag/
Drums
148.00 Keep container tightly closed.
Keep container in a cool, well-
ventilated area.
30 Toluene Flammable Drums 53630.00 Keep away from heat, sparks,
and flame. Keep away from
sources of ignition. Keep
container closed
31 Xylene Flammable Drums 240.00 Keep away from heat, sparks,
and flame. Keep away from
sources of ignition. Keep
container closed
32 Iso Propyl
Acetate
Flammable Drums 8655.00 Keep away from heat. Keep
away from sources of ignition.
Keep container tightly closed.
Keep in a cool, well-ventilated
place
Page 170 of 177
ANNEXURE - IX
_________________________________________________________________________
SOCIO - ECONOMIC IMPACTS
1) Employment Opportunities
The manpower requirement for the proposed expansion project is being expected to
generate some permanent jobs and secondary jobs for the operation and maintenance of
plant. This will increase direct / indirect employment opportunities and ancillary business
development to some extent for the local population.
This phase is expected to create a beneficial impact on the local socio-economic
environment.
2) Industries
Required raw materials and skilled and unskilled laborers will be utilized maximum from the
local area. The increasing industrial activity will boost the commercial and economical status
of the locality, to some extent.
3) Public Health
The company regularly examines, inspects and tests its emission from sources to make sure
that the emission is below the permissible limit. Hence, there will not be any significant
change in the status of sanitation and the community health of the area, as sufficient
measures have been taken and proposed under the EMP.
4) Transportation and Communication
Since the existing factory is having proper linkage for the transport and communication, the
development of this project will not cause any additional impact.
In brief, as a result of the proposed there will be no adverse impact on sanitation,
communication and community health, as sufficient measures have been proposed to be
taken under the EMP. The proposed scenario is not expected to make any significant change
in the existing status of the socio - economic environment of this region.
Page 171 of 177
ANNEXURE - X
_________________________________________________________________________
PROPOSED TERMS OF REFERENCE FOR EIA STUDIES
1. Project Description
• Justification of project.
• Promoters and their back ground
• Project site location along with site map of 5 km area and site details providing various
industries, surface water bodies, forests etc.
• Project cost
• Project location and Plant layout.
• Existing infrastructure facilities
• Water source and utilization including proposed water balance.
• List of Products & their capacity
• Details of manufacturing process of proposed products
• List of hazardous chemicals
• Mass balance of each product
• Storage and Transportation of raw materials and products.
2. Description of the Environment and Baseline Data Collection
• Micrometeorological data for wind speed, direction, temperature, humidity and rainfall
in 10 km area.
• Existing environmental status Vis a Vis air, water, noise, soil in 10 km area from the
project site.
• Ground water quality at 8 locations within 10 km.
• Complete water balance
3. Socio Economic Data
• Existing socio-economic status, land use pattern and infrastructure facilities available in
the study area were surveyed.
4. Impacts Identification And Mitigatory Measures
• Identification of impacting activities from the proposed project during construction and
operational phase.
• Impact on air and mitigation measures including green belt
• Impact on water environment and mitigation measures
• Soil pollution source and mitigation measures
• Noise generation and control.
• Solid waste quantification and disposal.
• Control of fugitive emissions
5. Environmental Management Plan
• Details of pollution control measures
• Environment management team
• Proposed schedule for environmental monitoring including post project
Page 172 of 177
6. Risk Assessment
• Objectives, Philosophy and methodology of risk assessment
• Details on storage facilities
• Process safety, transportation, fire fighting systems, safety features and emergency
capabilities to be adopted.
• Identification of hazards
• Consequence analysis
• Recommendations on the basis of risk assessment done
• Disaster Management Plan.
7. Information for Control of Fugitive Emissions
8. Information on Rain Water Harvesting
9. Green Belt Development plan
Page 173 of 177
ANNEXURE - XI
_________________________________________________________________________
COPY OF PLOT ALLOTMENT LETTER
Page 174 of 177
ANNEXURE - XII
_________________________________________________________________________
COPY OF GIDC WATER SUPPLY CERTIFICATE
Page 175 of 177
ANNEXURE - XIII
_________________________________________________________________________
MEMBERSHIP CERTIFICATE OF CETP (M/s. PETL)
Page 176 of 177
ANNEXURE - XIV
_________________________________________________________________________
MEMBERSHIP CERTIFICATE OF COMMON HAZARDOUS WASTE DISPOSAL FACILITY &
COMMON INCINERATION FACILITY (M/s. BEIL)
Page 177 of 177
ANNEXURE - XV
_________________________________________________________________________
TOPOSHEET