Supporting Information
Diastereoselective synthesis of CF3-oxazinoquinolines in waterVasiliy M. Muzalevskiya, Kseniya V. Belyaevab, Boris A. Trofimov*b, Valentine G. Nenajdenko*a
a M. V. Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory 1, Moscow, 119991 Russian Federation
bA. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., Irkutsk, 664033
Russian Federation; Fax: (395-2)41-93-46
Table of contents
General remarks S2
Reaction of CF3-ynones and quinolines in water (general procedure) S2
Characterization data of CF3-oxazinoquinolines 3 S2-S8
Epimerization of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a) S8
(3R*,4aR*)-3-Ethoxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinoline (4) S8
Reaction of oxazine (3a) with methyl 2-mercaptoacetate S9
Transformation of oxazine (3a) into 2-phenylquinoline (6) S9
Transformation of oxazine (3a) into 2,2,2-trifluoro-1-(2-phenylquinolin-3-yl)ethanone (7) S10
Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a) to form 8 and 9
S11
Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)
to form 11 S11
Copies of all NMR spectra S13-S83
S1
Electronic Supplementary Material (ESI) for Green Chemistry.This journal is © The Royal Society of Chemistry 2019
General remarks. 1H, 13C and 19F NMR spectra were recorded on Bruker AVANCE 400 MHz spectrometer
in CD3CN and CDCl3 at 400, 100 and 376 MHz respectively. Chemical shifts (δ) in ppm are reported with
the use of the residual CHD2CN and chloroform signals (1.94 and 7.25 for 1H and 77.0 for 13C) as internal
reference. The 19F chemical shifts were referenced to C6F6, (-162.9 ppm). HRMS (ESI-TOF) spectra were
measured with an Orbitrap Elite instrument. TLC analysis was performed on “Merck 60 F254” plates. All
reagents were of reagent grade and were used as such or distilled prior to use. CF3-ynones 2 were prepared as
reported previously1. Melting points were determined on an Electrothermal 9100 apparatus. The NMR and
m.p. data of compounds 3 (with the exception of 3i,j,k,n, which is a new compound) are in agreement with
those in the literature2.
Reaction of CF3-ynones and quinolines in water (general procedure): A 4 mL vial with a screw cap was
charged with water (0.5 mL), quinoline 1 (0.475 mmol, 0.95 equiv.) and then CF3-ynone 2 (0.5 mmol, 1
equiv.) was added at vigorous stirring. The reaction mixture was stirred at room temperature for 1-2 h (TLC
or 19F NMR control; 24 h for quinoline 1c and for ketone 2i). Excess water was decanted; the residue was
dissolved in ethyl acetate (0.5 mL) and dried over Na2SO4 (directly in the reaction vial). The solution was
transferred into a round bottomed flask and the product crystallized by addition of appropriate amount of
heptane (2-3 mL). The mother liquor was decanted, the crude product was dried under reduced pressure to
give pure (3R*,4aR*)-isomer of 3.
(3R*,4aR*)-1-Phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]-quinolin-3-ol (3a). Obtained from
quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5 mmol). White
powder, m.p. 154-156 C (heptane), yield 0.153 g (93%). For multi gram scale
reaction (60 equivalents of water): compound 3a was obtained from quinoline 1a
(0.613 g, 4.75 mmol), water (5 mL) and acetylene 2a (0.995 g, 5 mmol). Ethyl acetate
(2.5 mL) and heptane (8 mL) were used for isolation of 3a. White powder, m.p. 154-
156 C (heptane), yield 1.480 g (90%). Calculation of E-factor for multi gram scale reaction (60 equiv.):
E=[m(EtOAc)+m(heptane)+m(water)+m(Na2SO4)+m(1a)+m(2a)]/m(3a)=(2.25+5.44+5+0.30+0.613+0.995)/
1.480=9.86. For multi gram scale reaction (3 equivalents of water): compound 3a was obtained from
quinoline 1a (1.612 g, 12.5 mmol), water (0.675 mL) and acetylene 2a (2.612 g, 13.1 mmol). Ethyl acetate (6
mL) and heptane (20 mL) were used for first crystallization. For purification of material obtained from the
mother liquor ethyl acetate (2.5 mL) and heptane (8 mL) were used. White powder, m.p. 154-156 C
(heptane), yield 3.878 g (90%). Calculation of E-factor for multi gram scale reaction (3 equiv.):
1 V. M. Muzalevskiy, A. Yu. Rulev, A. R. Romanov, E. V. Kondrashov, I. A. Ushakov, V. A. Chertkov and V. G. Nenajdenko, J. Org. Chem., 2017, 82, 7200.2 B. A. Trofimov, K. V. Belyaeva, L. P. Nikitina, A. V. Afonin, A. V. Vashchenko, V. M. Muzalevskiy and V. G. Nenajdenko, Chem. Commun., 2018, 54, 2268.
S2
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
io
p
m
4aH
E=[m(EtOAc)+m(heptane)+m(water)+m(Na2SO4)+m(1a)+m(2a)]/m(3a)=(7.667+19.152+0.675+0.70+1.613
+2.612)/3.878=8.36. Calculation of E-factor (approximate value) for the reaction in MeCN2:
E=[m(MeCN)+m(water)+m(1a)+m(2a)+m(Sicagel)+m(eluents)]/m(3a)=(2.37+0.009+0.061+0.099+25.0+26
6…399 (~200-300 mL of eluents was used))/0.148=1983…2867~ 2000-3000.1H NMR (400.13 MHz, CD3CN): δ 7.56-7.54 (m, 2H, Ho from Ph), 7.47-7.39 (m, 3H, Hm,p from Ph), 7.25
(dd, 3J = 7.1 Hz, 4J = 1.9 Hz, 1H, H-7), 7.01 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.90 (td, 3J = 7.4 Hz, 4J = 1.8 Hz,
1H, H-9), 6.85 (td, 3J = 7.3 Hz, 4J = 1.2 Hz, 1H, H-8), 6.31 (d, 3J = 7.8 Hz, 1H, H-10), 6.12 (dd, 3J5,6 = 9.8
Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.03 (s, 1H, H-2), 5.66 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.55 (s, 1H, OH) ppm.19F NMR (376.50 MHz, CD3CN): δ -82.0 (CF3) ppm. 1H NMR (400.13 MHz, CDCl3): δ 7.54-7.52 (m, 2H, Ho from Ph), 7.43-7.35 (m, 3H, Hm,p from Ph), 7.18 (dd, 3J = 7.2 Hz, 4J = 0.8 Hz, 1H, H-7), 6.95 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.90 (td, 3J = 7.7 Hz, 4J = 1.1 Hz, 1H, H-
9), 6.84 (t, 3J = 7.2 Hz, 1H, H-8), 6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.04 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H,
H-5), 5.97 (s, 1H, H-2), 5.68 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 3.19 (s, 1H, OH) ppm.
(3R*,4aR*)-1-(4-Methylphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3b)
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2b (0.106 g, 0.5
mmol). Light-brown powder, m.p. 132-134 C (heptane), RF(CH2Cl2-MeOH
100:1) = 0.27, yield 0.163 g (96%).1H NMR (400.1 MHz, CD3CN): δ 7.43 (d, 3J = 8.1 Hz, 2H, H-2’,6’), 7.24 (dd, 3J =
7.1 Hz, 4J = 1.6 Hz, 1H, H-7), 7.22 (d, 3J = 8.1 Hz, 2H, H-3’,5’), 6.99 (d, 3J5,6 = 9.7
Hz, 1H, H-6), 6.91-6.83 (m, 2H, H-9, H-8), 6.33 (d, 3J = 8.0 Hz, 1H, H-10), 6.11 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 =
4.8 Hz, 1H, H-5), 5.97 (s, 1H, H-2), 5.63 (d, 3J = 4.7 Hz, 1H, H-4a), 5.54 (br s, 1H, OH), 2.35 (s, 3H, Me)
ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.
(3R*,4aR*)-1-(3,4-Dimethylphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3c).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2c (0.113 g, 0.5
mmol). Light-brown powder, m.p. 95-97 C (heptane), RF(CH2Cl2-MeOH 100:1) =
0.30, yield 0.169 g (95%).1H NMR (400.1 MHz, CD3CN): δ 7.34 (s, 1H, H-2’), 7.24-7.22 (m, 2H, H-7, H-
6’), 7.16 (d, 3J = 7.8 Hz, 1H, H-5’), 6.99 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.92-6.83 (m,
2H, H-9, H-8), 6.34 (d, 3J = 7.9 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.5 Hz, 3J4a,5 = 4.6 Hz, 1H, H-5), 5.93 (s, 1H,
H-2), 5.61 (d, 3J4a,5 = 4.5 Hz, 1H, H-4a), 5.47 (br s, 1H, OH), 2.27 (s, 3H, Me), 2.24 (s, 3H, Me) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.
S3
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4a
Me
1'2'3'
4' 5'6'
H
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4a
Me
1'2'3'
4' 5'6'
H
Me
(3R*,4aR*)-1-(4-(tert-Butyl)phenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3d).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2d (0.127 g, 0.5
mmol). Light-brown powder, m.p. 104-106 C (heptane), RF(CH2Cl2-MeOH
100:1) = 0.27, yield 0.182 g (96%). 1H NMR (400.1 MHz, CD3CN): δ 7.42-7.48
(m, 4H, H-2’,3’,5’,6’), 7.24 (dd, 3J = 7.2 Hz, 4J = 1.6 Hz, 1H, H-7), 7.00 (d, 3J5,6 =
9.7 Hz, 1H, H-6), 6.90-6.83 (m, 2H, H-9, H-8), 6.32 (d, 3J = 7.8 Hz, 1H, H-10),
6.10 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 5.98 (s, 1H, H-2), 5.63 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.51
(s, 1H, OH), 1.31 (s, 9H, 3Me from t-Bu) ppm.19F NMR (376.3 Hz, CD3CN): δ -82.0 (CF3) ppm.
(3R*,4aR*)-1-(4-Methoxyphenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3e).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2e (0.114 g, 0.5
mmol). Light-brown powder, m.p. 95-97 C (heptane), RF(CH2Cl2-MeOH 100:1)
= 0.43, yield 0.176 g (99%).1H NMR (400.1 MHz, CD3CN): δ 7.46 (d, 3J = 8.9 Hz, 2H, H-2’,6’), 7.24 (dd, 3J =
7.3 Hz, 4J = 1.5 Hz, 1H, H-7), 7.00 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.93 (d, 3J = 8.9
Hz, 2H, H-3’,5’), 6.90-6.83 (m, 2H, H-9, H-8), 6.35 (d, 3J = 8.0 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.8 Hz, 3J4a,5
= 4.9 Hz, 1H, H-5), 5.92 (s, 1H, H-2), 5.63 (d, 3J4a,5 = 4.7 Hz, 1H, H-4a), 5.58 (br s, 1H, OH), 3.79 (s, 3H,
OMe) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.
(3R*,4aR*)-1-[4-(Methylthio)phenyl]-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3f).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2f (0.122 g, 0.5
mmol). Light-brown powder, m.p. 98-100 C (heptane), RF(CH2Cl2-MeOH 100:1)
= 0.20, yield 0.178 g (96%).1H NMR (400.1 MHz, CD3CN): δ 7.45 (d, 3J = 8.4 Hz, 2H, H-2’,6’), 7.26-7.21 (m,
3H, H-7, H-3’,5’), 6.99 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.94-6.84 (m, 2H, H-9, H-8),
6.33 (d, 3J = 8.1 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.6 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 5.98 (s, 1H, H-2), 5.61 (d, 3J4a,5 = 4.3 Hz, 1H, H-4a), 5.54 (br s, 1H, OH), 2.47 (s, 3H, MeS) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.
(3R*,4aR*)-1-(4-Chlorophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3g).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2g (0.116 g, 0.5
mmol). Light-brown powder, m.p. 91-93 C (heptane), RF(CH2Cl2-MeOH 100:1) =
0.70, yield 0.159 g (88%).
S4
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
t-Bu
1'2'3'
4' 5'6'
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
O
1'2'3'
4' 5'6'
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
Cl
1'2'3'
4' 5'6'
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
S
1'2'3'
4' 5'6'
1H NMR (400.1 MHz, CD3CN): δ 7.53 (d, 3J = 8.7 Hz, 2H, H-2’,6’), 7.42 (d, 3J = 8.7 Hz, 2H, H-3’,5’), 7.25
(dd, 3J = 7.4 Hz, 4J = 1.4 Hz, 1H, H-7), 6.99 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.95-6.85 (m, 2H, H-9, H-8), 6.27
(d, 3J = 8.0 Hz, 1H, H-10), 6.11 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.03 (s, 1H, H-2), 5.62 (d, 3J =
4.8 Hz, 1H, H-4a), 5.55 (br s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.0 (CF3) ppm.
(3R*,4aR*)-1-(4-Bromophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3h).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2h (0.138 g, 0.5
mmol). Light-brown powder, m.p. 128-130 C (heptane), RF(CH2Cl2-MeOH 100:1)
= 0.73, yield 0.192 g (95%).1H NMR (400.1 MHz, CD3CN): δ 7.57 (d, 3J = 8.6 Hz, 2H, H-3’,5’), 7.45 (d, 3J =
8.6 Hz, 2H, H-2’,6’), 7.25 (dd, 3J = 7.3 Hz, 4J = 1.2 Hz, 1H, H-7), 7.00 (d, 3J5,6 =
9.7 Hz, 1H, H-6), 6.95-6.85 (m, 2H, H-9, H-8), 6.27 (d, 3J = 8.0 Hz, 1H, H-10), 6.10 (dd, 3J5,6 = 9.7 Hz, 3J4a,5
= 4.8 Hz, 1H, H-5), 6.04 (s, 1H, H-2), 5.61 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.56 (s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -81.9 (CF3) ppm.
(3R*,4aR*)-1-(2-Chlorophenyl)-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3i).
Obtained from quinoline 1a (0.061 g, 0.475 mmol) and acetylene 2i (0.116 g, 0.5
mmol). Light-brown powder, m.p. 100-102 C (heptane), yield 0.165 g (91%).1H NMR (400.1 MHz, CD3CN): δ 7.54-7.49 (m, 2H), 7.41 (td, 3J = 7.7 Hz, 4J = 1.8
Hz, 1H), 7.35 (td, 3J = 7.4 Hz, 4J = 1.4 Hz, 1H), 7.23 (dd, 3J = 7.4 Hz, 4J = 1.2 Hz,
1H, H-7), 6.97 (d, 3J5,6 = 9.8 Hz, 1H, H-6), 6.94-6.90 (m, 1H, H-9), 6.86-6.81 (m, 1H,
H-8), 6.36 (d, 3J = 8.1 Hz, 1H, H-10), 6.09 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.6 Hz, 1H, H-5), 5.94 (s, 1H, H-2),
5.71 (d, 3J = 4.3 Hz, 1H, H-4a), 5.53 (br s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -81.8 (CF3) ppm.13C NMR (100.6 Hz, CD3CN): δ 145.0 (C-1), 137.4, 134.4, 133.0, 131.79, 131.77, 131.5, 130.2, 129.9,
129.1, 128.6, 123.6 (q, 1JCF = 285.3 Hz, CF3), 122.1, 121.9, 121.6, 119.1, 116.4, 116.0, 92.7 (q, 2JCF = 32.8
Hz, C-3), 78.8 (C-4a) ppm.
HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12ClF3NO+: 362.0554; found: 362.0554; m/z [M+H]+ Calcd
for C19H14ClF3NO2+: 380.066; found: 380.0658.
(3R*,4aR*)-1-(2,3-Dihydrobenzo[b][1,4]dioxin-7-yl)-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-
a]quinolin-3-ol (3j). Obtained from quinoline 1a (0.061 g, 0.475 mmol) and
acetylene 2j (0.114 g, 0.5 mmol). Yellow-brown powder, m.p. 114-116 C
(heptane), yield 0.190 g (99%).
S5
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
Br
1'2'3'
4'5'
6'
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
1'6'5'
4'3'
2' Cl
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
4aH
1'2'3'
4' 5'6'
O
O
1H NMR (400.1 MHz, CD3CN): δ 7.24 (dd, 3J = 7.5 Hz, 4J = 1.5 Hz, 1H, H-7), 7.03-6.92 (m, 4H, H-6, H-9,
H-5’,6’), 6.88-6.84 (m, 2H, H-8, H-2’), 6.36 (d, 3J = 8.2 Hz, 1H, H-10), 6.08 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.8
Hz, 1H, H-5), 5.89 (s, 1H, H-2), 5.58 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.34 (br s, 1H, OH), 4.27-4.21 (m, 4H,
OCH2CH2O) ppm.13C NMR (100.6 Hz, CD3CN): δ 148.0, 146.2, 144.9 (C-1), 138.3, 130.4, 129.5, 128.8, 128.7, 123.5 (q, 1JCF
= 285.5 Hz, CF3), 122.5, 121.4, 120.3, 119.2, 118.6, 118.0, 116.0, 111.2, 93.0 (q, 2JCF = 32.8 Hz, C-3), 78.3
(C-4a), 65.3 (CH2), 65.0 (CH2) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.2 (CF3) ppm.
HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C21H15F3NO3+: 386.0999; found: 386.0999; m/z [M+H]+ Calcd
for C21H17F3NO4+: 404.1104; found: 404.1108.
(3R*,4aR*)-9-Chloro-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3k).
Obtained from quinoline 1b (0.078 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5
mmol). Pale yellow powder, m.p. 146-148 oC (heptane), yield 0.169 g (94%). 1H
NMR (400.13 MHz, CD3CN): δ 7.59-7.54 (m, 2H, Ho from Ph), 7.49-7.41 (m, 3H,
Hm,p from Ph), 7.22 (d, 3J7,8 = 8.1 Hz, 1H, H-7), 6.99 (d, 3J5,6 = 9.8 Hz, 1H, H-6),
6.85 (dd, 3J7,8 = 8.1 Hz, 4J8,10 = 1.9 Hz, 1H, H-8), 6.28 (d, 4J8,10 = 1.5 Hz, 1H, H-
10), 6.13 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.07 (s, 1H, H-2), 5.67 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a),
5.49 (s, 1H, OH) ppm.13C NMR (100.6 Hz, CD3CN): δ 148.0 (C-1), 139.2, 135.0, 134.2, 131.1, 130.2, 130.1, 129.5, 127.3, 123.5
(q, 1JCF = 285.1 Hz, CF3), 121.4, 121.3, 119.7, 117.6, 113.3, 93.0 (q, 2JCF = 33.0 Hz, C-3), 78.2 (C-4a) ppm.19F NMR (376.50 MHz, CD3CN): δ -82.0 (CF3) ppm.
HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12ClF3NO+: 362.0554; found: 362.0555; m/z [M+H]+ Calcd
for C19H14ClF3NO2+: 380.066; found: 380.0655.
(3R*,4aR*)-8-Chloro-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3l).
Obtained from quinoline 1c (0.078 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5
mmol). White powder, m.p. 138-140 oC (heptane), yield 0.175 g (97%). 1H NMR
(400.13 MHz, CDCl3): δ 7.53-7.50 (m, 2H, Ho from Ph), 7.44-7.36 (m, 3H, Hm,p
from Ph), 7.16 (d, 4J7,9 = 2.4 Hz, 1H, H-7), 6.86 (d, 3J5,6 = 8.9 Hz, 1H, H-6), 6.85
(d, 3J9,10 = 8.8 Hz, 1H, H-9), 6.28 (d, 3J9,10 = 8.8 Hz, 1H, H-10), 6.08 (dd, 3J5,6 =
9.8 Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.00 (s, 1H, H-2), 5.67 (d, 3J4a,5 = 4.5 Hz, 1H, H-4a), 3.22 (s, 1H, OH) ppm. 19F NMR (376.3 MHz, CDCl3): δ -84.2 (CF3) ppm.
(3R*,4aR*)-3-Hydroxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-
a]quinoline-6-carbonitrile (3m). Obtained from quinoline 1f (0.073 g, 0.475 mmol)
S6
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
io
p
m
4aH
Cl
N O
CF3
OH1
23
4
567
8
9 10 10a11
6a
io
p
m
4aH
Cl
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
io
p
m
4a
CN
H
and acetylene 2a (0.099 g, 0.5 mmol). Light-brown powder, m.p. 107-110 C (heptane), RF(CH2Cl2-MeOH
100:1) = 0.30, yield 0.170 g (97%).1H NMR (400.1 MHz, CD3CN): δ 7.56-7.52 (m, 2H, Ho from Ph), 7.46-7.39 (m, 3H, Hm,p from Ph), 7.31 (d, 3J5,6 = 10.0 Hz, 1H, H-6), 7.21 (dd, 3J = 7.7 Hz, 4J = 1.0 Hz, 1H, H-8), 7.00 (pseudo-t, 3J ~ 8 Hz, 1H, H-9),
6.59 (pseudo-d, 3J ~ 8 Hz, 1H, H-10), 6.38 (dd, 3J5,6 = 9.9 Hz, 3J4a,5 = 4.8 Hz, 1H, Н-5), 6.10 (s, 1H, H-2),
5.72 (d, 3J4a,5 = 5.0 Hz, 1H, H-4a), 5.72 (br. s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.2 (CF3) ppm.
(3R*,4aR*)-8-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-a]quinolin-3-ol (3n).
Obtained from quinoline 1d (0.098 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5
mmol). White powder, m.p. 136-138 oC (heptane), yield 0.195 g (97%).1H NMR (400.1 MHz, CD3CN): δ 7.55-7.53 (m, 2H, Ho from Ph), 7.45-7.39 (m,
4H, Hm,p from Ph, H-7), 7.00 (dd, 3J9,10 = 8.8 Hz, 4J = 2.4 Hz, 1H, H-9), 6.95 (d, 3J5,6 = 9.9 Hz, 1H, H-6), 6.21 (d, 3J9,10 = 8.8 Hz, 1H, H-10), 6.16 (dd, 3J5,6 = 9.8
Hz, 3J4a,5 = 4.8 Hz, 1H, H-5), 6.02 (s, 1H, H-2), 5.64 (d, 3J4a,5 = 4.8 Hz, 1H, H-4a), 5.59 (s, 1H, OH) ppm. 13C NMR (100.16 Hz, CD3CN): δ 148.2 (C-1), 137.3 (C-10a), 135.1 (Ci from Ph), 131.9 (C-6), 131.00 and
130.98 (Cp from Ph, C-6), 130.1 (Cm from Ph), 129.3 (C-9), 127.3 (Co from Ph), 127.3 (C-7), 124.5 (C-8),
123.5 (q, 1JCF = 284.9 Hz, CF3), 120.8 (C-5), 119.7 (C-10), 113.3 (C-6a), 113.0 (C-2), 93.0 (q, 2JCF = 33.2
Hz, C-3), 78.2 (C-4a) ppm.19F NMR (376.50 Hz, CD3CN): δ -82.1 (CF3) ppm.
HRMS (ESI-TOF): m/z [M-OH]+ Calcd for C19H12BrF3NO+: 406.0049; found: 406.0052; m/z [M+H]+ Calcd
for C19H14BrF3NO2+: 424.0155; found: 424.0157.
(3R*,4aR*)-6-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3o).
Obtained from quinoline 1e (0.099 g, 0.475 mmol) and acetylene 2a (0.099 g, 0.5
mmol). Light-brown powder, m.p. 115-117 C (heptane), RF(CH2Cl2-MeOH 100:1) =
0.71, yield 0.199 g (99%).1H NMR (400.1 MHz, CD3CN): δ 7.55-7.53 (m, 2H, Ho from Ph), 7.45-7.36 (m, 4H,
H-6, Hm,p from Ph), 7.10 (d, 3J = 8.1 Hz, 1H, H-8), 6.77 (t, 3J = 8.1 Hz, 1H, H-9), 6.33
(d, 3J = 8.1 Hz, 1H, H-10), 6.25 (dd, 3J5,6 = 9.8 Hz, 3J4a,5 = 4.7 Hz, 1H, Н-5), 6.08 (s,
1H, H-2), 5.65 (d, 3J = 4.7 Hz, 1H, H-4a), 5.61 (br. s, 1H, OH) ppm.19F NMR (376.3 MHz, CD3CN): δ -82.1 (CF3) ppm.
(3R*,4aR*)-5-Bromo-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]-oxazino[3,2-
a]quinolin-3-ol (3p). Obtained from quinoline 1g (0.099 g, 0.475 mmol) and acetylene
S7
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
io
p
m
4aH
Br
N O
CF3
OH1
23
4
567
8
910 10a
11
6a
io
p
m
4a
Br
H
N O
CF3
OH1
23
4
5678
910 10a
11
6a
io
p
m
4a
BrH
2a (0.099 g, 0.5 mmol). Light-yellow powder, m.p. 68-70 oC (heptane), yield 0.186 g (92%). 1H NMR (400.1 MHz, CD3CN): δ 7.58-7.55 (m, 2H, Ho from Ph), 7.48-7.38 (m, 4H, Hm and Hp from Ph, H-
6), 7.22 (dd, 3J = 7.2 Hz, 4J = 1.7 Hz, 1H, H-7), 6.96-6.86 (m, 2H, H-9, H-8), 6.32 (d, 3J9,10 = 8.1 Hz, 1H, H-
10), 6.06 (s, 1H, H-2), 5.74 (s, 1H, H-4a), 5.67 (br. s, 1H, OH) ppm. 13C NMR (100.16 Hz, CD3CN): δ 148.0 (C-2), 136.9 (C-11a), 135.1 (Ci from Ph), 132.6 (C-6), 131.1 (Cp
from Ph), 130.1 (Cm from Ph), 130.0 (C-9), 128.4 (C-7), 127.4 (Co from Ph), 123.3 (q, 1JCF = 282.9 Hz, CF3),
122.1 (C-6a), 122.0 (C-8), 118.9 (C-10), 113.0 (C-5), 112.4 (C-2), 93.4 (q, 2JCF = 33.2 Hz, C-3), 83.3 (C-4a)
ppm.19F NMR (376.5 MHz, CD3CN): δ -82.0 (CF3) ppm.
(6aR*,8R*)-10-Phenyl-8-(trifluoromethyl)-6aH,8H-[1,3]oxazino[3,2-a][1,8]naphthyridin-8-ol (3q).
Obtained from 1,8-naphthyridine 1h (0.062 g, 0.475 mmol) and acetylene 2a (0.099 g,
0.5 mmol). Pale brown crystals, m.p. 145-147 C (heptane), yield 0.155 g (94%). 1H NMR (400.1 MHz, CD3CN): δ 7.73 (dd, 3J = 4.8 Hz, 4J = 1.6 Hz, 1H), 7.55 (dd, 3J =
7.4 Hz, 4J = 1.5 Hz, 1H), 7.49-7.45 (m, 2H, Ho from Ph), 7.37-7.32 (m, 3H, Hm,p from Ph), 7.00 (d, 3J = 9.7
Hz, 1H), 6.82 (dd, 3J = 7.4 Hz, 3J = 5.0 Hz, 1H), 6.16 (dd, 3J = 9.7 Hz, 3J = 4.7 Hz, 1H), 5.96 (s, 1H), 5.81 (d, 3J = 4.6 Hz, 1H), 5.65 (s, 1H, OH) ppm.
19F NMR (376.5 MHz, CD3CN): δ -82.0 (CF3) ppm.
Epimerization of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a).
Oxazine 3a (0.050 g, 0.145 mmol) was dissolved in t-BuOH (1 mL) and H2O (0.5
mL) was added. The solution formed was left overnight. The volatiles were
evaporated in vacuo to give mixture of 3a ((3R*,4aR)-isomer) and 3a’ ((3S*,4aR)-
isomer) (0.050 g, ~100%) as light brown powder, m.p. 142-144 oC. (3R*,
4aR*):(3S*, 4aR*)-isomers ratio is 87:13. 1H NMR (400.13 MHz, CDCl3): δ 7.54-7.52 (m, 2H, Ho from Ph), 7.43-7.35 (m, 3H, Hm,p from Ph), 7.0 (d, 3J
= 7.2 Hz, 1H, H-7), 6.97-6.81 (m, 3H, H-6, H-9, H-8), 6.33 (d, 3J = 7.8 Hz, 1H, H-10), 6.04 (dd, 3J5,6 = 9.3
Hz, 3J4a,5 = 4.4 Hz, 1H, H-5), 5.97 (s, 1H, H-2), 5.68 (br s, 1H, H-4a), 3.19 (s, 1H, OH) ppm.19F NMR (376.50 Hz, CDCl3): δ -84.3 (CF3) ppm;
(4S*, 5aR*)-3a’: 1H NMR (400.13 MHz, CDCl3): 6.09 (dd, 3J5a,6 = 4.7 Hz, 3J6,7 = 9.8 Hz, 1H, H-6), 5.62 (d, 3J5a,6 = 4.7 Hz, 1H, H-5a) ppm. The other signals are identical to those of major isomer.19F NMR (376.50 Hz, CDCl3): δ -81.1 (CF3) ppm.
(3R*,4aR*)-3-Ethoxy-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinoline (4).
Oxazine 3a (0.100 g, 0.29 mmol) was dissolved in absolute EtOH (1 mL) and the
solution formed was left for 1 day. The volatiles were evaporated in vacuo to give 4
(0.106 g, 98%) as light yellow powder, m.p. 130-132 oC. S8
N N O
Ph CF3
OH
H
N O
CF3
OH
3a
11
1
2 3
4
567
89 10a10
6a
io
p
m
4a
N O
CF3
OEt
1
1
2 3
4
567
8
911a10
6a
io
p
m
4a
1H NMR (400.13 MHz, CD3CN): δ 7.56-7.54 (m, 2H, Ho from Ph), 7.47-7.38 (m, 3H, Hm,p from Ph), 7.25
(dd, 3J = 7.1 Hz, 4J = 1.8 Hz, 1H, H-7), 7.01 (d, 3J5,6 = 9.7 Hz, 1H, H-6), 6.91-6.83 (m, 2H, H-9, H-8), 6.32
(d, 3J = 7.8 Hz, 1H, H-10), 6.20 (dd, 3J5,6 = 9.7 Hz, 3J4a,5 = 4.7 Hz, 1H, H-5), 6.07 (s, 1H, H-2), 5.69 (d, 3J4a,5
= 4.8 Hz, 1H, H-4a), 3.91-3.78 (m, 2H, CH2), 1.24 (t, 3H, 3J = 7.0 Hz, CH3) ppm.19F NMR (376.50 MHz, CD3CN): δ -80.1 (CF3) ppm. 13C NMR (100.6 Hz, CD3CN): δ 150.5, 138.1, 135.4, 131.1, 130.4, 130.1, 129.6, 128.9, 127.42, 127.36,
123.2 (q, 1JCF = 286.2 Hz, CF3), 121.6, 119.0, 117.9, 112.8, 95.6 (q, 2JCF = 31.7 Hz), 80.3, 60.0, 15.8 ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C21H18F3NO2+: 374.1362; found: 374.1369.
Reaction of oxazine (3a) with methyl 2-mercaptoacetate. A 4 mL vial with a screw cup was charged with
with oxazine 3a (0.071 g, 0.2 mmol), solution of methyl 2-mercaptoacetate in
MeOH (1 mL, 0.5 M, 0.5 mmol) and left at room temperature for 72 h. MeOH was
evaporated to give 0.093 g of light brown oil, consisting of quinoline, methyl 2-
((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (85:15 mixture of
isomers) and dimethyl 2,2'-disulfanediyldiacetate (MeCO2-CH2-S-S-CH2CO2Me
appeared due to oxidation of methyl 2-mercaptoacetate by oxygen) in molar ratio 1:1:0.22. Compound 5,
major isomer: 1H NMR (400.13 MHz, CDCl3): δ 7.40-7.42 (m, 2H, Ar), 7.21-7.25 (m, 3H, Ar), 6.57 (s, 1H,
C=CH), 3.52 (s, 3H, OCH3), 3.31 (s, 2H, SCH2). 13C NMR (100.6 MHz, CDCl3): δ 177.3 (q, С-CF3, J =
35.0), 171.3, 168.3, 136.7, 129.9, 128.8, 127.6, 116.1 (q, CF3, J = 290.4), 114.8, 52.5, 35.0. 19F NMR (376.50
Hz, CDCl3): δ -78.7. Minor isomer: 1H NMR (400.13 MHz, CDCl3): δ 7.41-7.44 (m, 2H, Ar), 7.30-7.32 (m,
3H, Ar), 6.47 (s, 1H, C=CH), 3.78 (s, 3H, OCH3), 3.66 (s, 2H, SCH2). 13C NMR (100.6 MHz, CDCl3): δ
130.2, 128.4, 127.9, 109.3, 52.9, other signals are identical to those of major isomer. 19F NMR (376.50 Hz,
CDCl3): δ -79.6. Quinoline: 1H NMR (400.13 MHz, CDCl3): δ 8.88 (dd, 3J = 4.3 Hz, 4J = 1.7 Hz, 1H), 8.14
(dd, 3J = 8.3 Hz, 4J = 1.1 Hz, 1H), 8.09 (d, 3J = 8.5 Hz, 1H), 7.78 (dd, 3J = 8.1 Hz, 4J = 0.7 Hz, 1H), 7.70-
7.66 (m, 1H), 7.53-7.49 (m, 1H), 7.38-7.34 (m, 1H). 13C NMR (100.6 MHz, CDCl3): δ 150.0, 147.7, 136.3,
129.5, 128.9, 128.2, 127.7, 126.6, 121.0. The NMR data of 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-
yl)thio)acetate 53 and quinoline4 are in agreement with those in the literature.
Transformation of oxazine (3a) into 2-phenylquinoline (6). A 4 mL vial with a screw cap was charged
with oxazine 3a (0.030 g, 0.087 mmol), water (0.5 mL) and NaOH (0.0104 g, 0.261 mmol). The reaction
mixture was heated at 80 C at stirring for 2 h. After cooling down to room temperature, the reaction mixture
was extracted with EtOAc (2x0.5 mL), combined organic phase was passed through a short silica gel pad
3 V. M. Muzalevskiy, A. A. Iskandarov, V. G. Nenajdenko, J. Fluorine Chem. 2018, 214, 13-16.4 T. Kaiya, N. Shiraiy, Y. Kawazoe, Chem. Pharm. Bull., 1986, 34, 881-885.
S9
MeO2C S O
Ph CF3
N
+
using heptane followed by heptane-EtOAc (15:1) as an eluents. Evaporation of volatiles afforded 6 as light
brown powder, m.p. 81-83 C (Lit. data: 82-84 C5), yield 0.016 g (90%).1H NMR (400.1 MHz, CDCl3): δ 8.22 (d, 3J = 8.6 Hz, 1H), 8.19-8.15 (m, 3H), 7.87 (d, 3J = 8.6 Hz, 1H), 7.83 (dd, 3J = 8.1 Hz, 4J = 0.7 Hz, 1H), 7.75-7.70 (m, 1H), 7.54-7.51
(m, 3H), 7.48-7.44 (m, 1H) ppm.13C NMR (100.6 MHz, CDCl3): δ 157.3, 148.2, 139.6, 136.7, 129.63, 129.61, 129.3,
128.8, 127.5, 127.4, 127.1, 126.2, 119.0 ppm. The NMR data are in agreement with those in the literature4.
Transformation of oxazine (3a) into 2,2,2-trifluoro-1-(2-phenylquinolin-3-yl)ethanone (7). A 4 mL vial
with a screw cap was charged with oxazine 3a (0.030 g, 0.087 mmol), MeCN (0.5
mL) and morpholine (0.0075 g, 0.087 mmol). The reaction mixture was heated at 80
C for 6 h and then volatiles were evaporated in vacuo. The residue was passed
through a short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an
eluents. Evaporation of volatiles afforded 7 as a pale yellow powder, m.p. 86-87 C,
yield 0.023 g (88%).1H NMR (400.1 MHz, CD3CN): δ 8.77 (s, 1H, H-4), 8.09 (m, 1H, H-8), 8.07 (m, 1H, H-5), 7.91 (m, 1H, H-
7), 7.68 (m, 1H, H-6), 7.56 (m, 2H, Ho from Ph), 7.49 (m, 3H, Hm,p from Ph) ppm.13C NMR (100.6 MHz, CD3CN): δ 185.4 (q, 2JCF = 36.0 Hz, C=O), 158.4 (C-2), 149.6 (C-8a), 140.8 (Ci from
Ph), 140.7 (q, 4JCF = 3.0 Hz, C-4), 134.3 (C-8), 130.3 (C-6), 130.2 (Cp from Ph, C-7), 130.1 (Co from Ph),
129.6 (Cm from Ph), 129.1 (C-5), 126.4 (C-4a), 126.0 (C-3), 117.1 (q, 1JCF = 291.7 Hz, CF3) ppm.19F NMR (376.5 MHz, CD3CN): δ -72.4 (CF3) ppm.1H NMR (400.1 MHz, CDCl3): δ 8.59 (s, 1H, H-4), 8.21 (d, 3J = 8.5 Hz, 1H, H-8), 7.97 (d, 3J = 8.1 Hz, 1H,
H-5), 7.91 (ptd, 3J ~ 8 Hz, 4J ~ 1 Hz, 1H, H-7), 7.68 (ptd, 3J ~ 8 Hz, 4J ~ 1 Hz, 1H, H-6), 7.59-7.57 (m, 2H,
Ho from Ph), 7.52-7.48 (m, 3H, Hm,p from Ph) ppm.13C NMR (100.6 MHz, CDCl3): δ 184.6 (q, 2JCF = 36.0 Hz, C=O), 157.7 (C-2), 148.7 (C-8a), 139.3 (Ci from
Ph), 139.0 (q, 4JCF = 3.0 Hz, C-4), 133.0 (C-8), 129.3 (C-6), 128.9 (Co from Ph), 128.8 (Cm from Ph), 128.7
(Cp from Ph, C-7), 127.9 (C-5), 125.9 (C-4a), 124.9 (C-3), 115.9 (q, 1JCF = 292.1 Hz, CF3) ppm.19F NMR (376.5 MHz, CDCl3): δ -73.7 (CF3) ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C17H11F3NO+: 302.0793; found: 302.0790.
5 N. Sudhapriya, A. Nandakumar, P. T. Perumal, RSC Advances, 2014, 4, 58476-58480.S10
N
O
CF3
12
345
6
78
4a
8a io p
m
N
Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)
to form 8 and 9. Three-necked round bottomed flask was charged with oxazine 3a
(0.105 g, 0.304 mmol), 10% Pd on carbon (0.032 g, 0.03 mmol, 10 mol%) and THF
(5 mL). The flask was evacuated and flushed with H2 from a balloon. The solution
formed was stirred 36 h and filtered off. The filter cake was washed with EtOAc
(3*3 mL), the volatiles were evaporated in vacuo. The residue was passed through a
short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an eluents. Evaporation of the
volatiles afforded a mixture 8 and 9 (75:25) as a colorless oil, yield 0.077 g (72%).
(3R*,4aR*)-1-Phenyl-3-(trifluoromethyl)-2,3,4a,5-tetrahydro-1H,6H-[1,3]oxazino[3,2-a]quinolin-3-ol
(8). 1H NMR (400.13 MHz, CDCl3): δ 7.44-7.29 (m, 5H, Ph), 7.08 (d, 3J = 7.3 Hz, 1H, H-7), 7.01 (pseudo-t, 3J ~ 8 Hz, 1H, H-9), 6.76 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.40 (d, 3J = 8.1 Hz, 1H, H-10), 5.53 (br s, 1H, H-
4a), 4.98 (dd, 3J = 11.8 Hz, 3J = 7.0 Hz, 1H, H-1), 3.10-2.93 (m, 1H), 2.79-2.67 (m, 3H), 2.37-2.30 (m, 1H),
2.33 (dd, 3J = 14.4 Hz, 3J = 11.8 Hz, 1H, H-2), 2.11-2.02 (m, 1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -88.0 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 143.4 (Cq), 142.2 (Cq), 129.1 (Cm from Ph), 128.5, 128.3, 127.5, 127.4,
127.0, 125.1 (Co from Ph), 123.2 (Cq), 122.3 (q, 1JCF = 285.5 Hz, CF3), 118.5, 112.9, 94.4 (q, 2JCF = 31.5 Hz,
C-3), 79.2 (C-4a), 55.5 (C-1), 33.4 (CH2), 25.9 (CH2), 21.6 (CH2) ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C19H18F3NO2+: 350.1362; found: 350.1351.
4-(3,4-diHydroquinolin-1(2H)-yl)-1,1,1-trifluoro-4-phenylbutan-2-ol (9). 1H NMR (400.13 MHz, CDCl3):
δ 7.44-7.29 (m, 5H, Ph), 6.64 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.47 (d, 3J = 8.1 Hz, 1H,
H-10), 5.61-5.37 (m, 1H), 4.14-4.10 (m, 1H), 3.10-2.93 (m, 2H), 2.79-2.67 (m, 1H),
2.50-2.43 (m, 1H), 2.37-2.30 (m, 2H), 2.29-2.22 (m, 1H), 1.87-1.84 (m, 2H) ppm.19F NMR (376.50 Hz, CDCl3): δ -80.8 (d, 3JHF = 6.8 Hz CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 145.8 (Cq), 140.0 (Cq), 129.7 (Cm from Ph), 129.0,
127.4, 127.3, 125.5 (Co from Ph), 122.8 (Cq), 125.4 (q, 1JCF = 281.7 Hz, CF3), 116.2, 111.0, 67.7 (q, 2JCF =
31.5 Hz, C-3), 54.3 (C-1), 42.1, 29.9 (CH2), 28.5 (CH2), 21.7 (CH2) ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C19H20F3NO+: 336.1570; found: 336.1560.
Hydrogenation of (3R*,4aR)-1-phenyl-3-(trifluoromethyl)-3H,4aH-[1,3]oxazino[3,2-a]quinolin-3-ol (3a)
to form 11. Three-necked round bottomed flask was charged with oxazine 3a
(0.105 g, 0.304 mmol), 10% Pd on carbon (0.034 g, 0.03 mmol, 10 mol%) and
MeOH (5 mL). The flask was evacuated and flushed with H2 from a balloon. The
solution formed was stirred 36 h and filtered off. The filter cake was washed with
EtOAc (3*3 mL), the volatiles were evaporated in vacuo. The residue was passed
S11
N O
CF3
O
11
11
1
2 3
4
567
89 10a10
6a
io
p
m
4a
N O
CF3
OH
8
11
1
2 3
4
567
89 10a10
6a
io
p
m
H
N
CF3
OH
9
through a short silica gel pad using heptane followed by heptane-EtOAc (10:1) as an eluents. Compounds 10
and 11 were isolated as a separate fractions.
3-Methoxy-1-phenyl-3-(trifluoromethyl)-4a,5-dihydro-3H,6H-[1,3]oxazino[3,2-a]quinoline (10).
Colorless oil, yield 0.011 g (10%).1H NMR (400.13 MHz, CDCl3): δ 7.39-7.27 (m, 5H, Ph), 7.11-7.09 (m, 1H), 6.84-6.78 (m, 2H), 6.22-6.20
(m, 1H), 5.60 (br s, 1H, H-4a), 5.33 (t, 3J = 7.7 Hz, 1H), 3.52 (s, 1H, MeO), 2.81-2.63 (m, 3H), 1.92-1.82 (m,
1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -81.5 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 149.3, 138.8, 134.7, 130.3, 129.6 128.6, 127.1, 126.8, 122.4 (q, 1JCF = 286.9
Hz, CF3), 121.5, 120.2, 105.6, 95.7 (q, 2JCF = 31.8 Hz, C-3), 83.0 (C-4a), 50.8 (MeO), 29.4(CH2), 24.7 (CH2)
ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C20H19F3NO2+: 362.1362; found: 362.1357.
3-Methoxy-1-phenyl-3-(trifluoromethyl)-2,3,4a,5-tetrahydro-1H,6H-[1,3]oxazino[3,2-a]quinoline (11).
A colorless oil solidifies at standing, m.p. 142-143 C, yield 0.093 g (84%). 1H NMR (400.13 MHz, CDCl3):
δ 7.41-7.29 (m, 5H, Ph), 7.05 (d, 3J = 7.3 Hz, 1H, H-7), 6.99 (pseudo-t, 3J ~ 8 Hz, 1H, H-9), 6.73 (pseudo-t, 3J ~ 7 Hz, 1H, H-8), 6.39 (d, 3J = 8.1 Hz, 1H, H-10), 5.52 (br s, 1H, H-4a), 4.90 (dd, 3J = 11.9 Hz, 3J = 7.0
Hz, 1H, H-1), 3.29 (s, 1H, MeO), 3.14-3.06 (m, 1H), 2.78-2.68 (m, 1H), 2.59 (dd, 3J = 14.3 Hz, 3J = 7.0 Hz,
1H, H-2), 2.45-2.39 (m, 1H), 2.33 (dd, 3J = 14.3 Hz, 3J = 11.9 Hz, 1H, H-2), 2.12-2.03 (m, 1H) ppm.19F NMR (376.50 Hz, CDCl3): δ -83.1 (CF3) ppm;13C NMR (100.16 Hz, CDCl3): δ 143.5 (Cq), 142.3 (Cq), 129.1 (Cm from Ph), 128.3, 127.5, 127.4, 125.2 (Co
from Ph), 122.8 (Cq), 122.7 (q, 1JCF = 289.3 Hz, CF3), 118.3, 112.8, 95.8 (q, 2JCF = 31.5 Hz, C-3), 79.0 (C-
4a), 55.8 (MeO), 50.5 (C-1), 34.6 (CH2), 26.3(CH2), 22.3 (CH2) ppm.
HRMS (ESI-TOF): m/z [M+H]+ Calcd for C20H21F3NO2+: 364.1519; found: 364.1522.
S12
23 Feb 2019
FW 345.3152 Formula C19H14F3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 22 Feb 2019 23:06:50File Name C:\BM_DATA\DOCS\Manuscr_Ultra\BM_2018\bm190222\BM-1499_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.01 1.98 0.97 0.88
Acetonitrile-d3
5.41
5.66
6.03
6.32
6.84
6.85
6.87
6.99
7.02
7.39
7.41
7.43
7.55
7.56
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
3.012.01 1.981.00 0.99 0.970.970.96 0.95 0.88
7.57
7.57
7.56
7.55
7.54
7.47
7.45
7.44
7.43
7.43
7.41
7.39
7.39
7.26 7.
247.
24 7.02 6.99
6.92 6.91
6.90 6.
886.
876.
876.
856.
856.
846.
83
6.32
6.30
6.13 6.12
6.11 6.10
6.03
5.66
5.65
5.41
1H NMR spectrum of 3a (400.1 MHz, CD3CN)
S13
12 Feb 2019
FW 345.3152 Formula C19H14F3NO2
Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM-1371_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000
OHN O
FF
F
H
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-81.
99
19F NMR spectrum of 3a (376.5 MHz, CD3CN)
S14
24 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 24 Jul 2019 17:34:04File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\190724\BM-1659-1_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.14 1.041.03 1.01
Chloroform-d
Chloroform-d
3.19
5.68
5.69
5.97
6.34
6.846.94
6.96
7.17
7.25
7.39
7.52
7.54
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)
3.142.07 1.041.03 1.03 1.001.00 1.001.000.98
Chloroform-d
5.685.69
5.97
6.03
6.046.05
6.07
6.326.34
6.82
6.84
6.86
6.886.
906.
926.
946.
96
7.17
7.19
7.25
7.357.
367.
377.
397.39
7.40
7.41
7.43
7.527.52
7.54
1H NMR spectrum of 3a in multi gram scale synthesis (400.1 MHz, CDCl3)
S15
12 Feb 2019
FW 359.3418 Formula C20H16F3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Sep 2018 19:18:46File Name C:\DOCS\OUTPUT_301\2018\09.ñåí òÿáðü\BM-1372\BM-1372_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
CH3
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.193.14 1.00 0.98
Acetonitrile-d3
2.35
5.62
5.63
5.97
6.85
6.98
7.00
7.21
7.23
7.42
7.44
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
3.142.10 2.041.00 1.000.99 0.98 0.98 0.88
7.44
7.42
7.25
7.25
7.23
7.21
7.00 6.98
6.91
6.89
6.89
6.88
6.87 6.
876.
86 6.85
6.84
6.83
6.83
6.34
6.32
6.12 6.11
6.10
6.08
5.97
5.63
5.62
5.54
1H NMR spectrum of 3b (400.1 MHz, CD3CN)
S16
12 Feb 2019
FW 359.3418 Formula C20H16F3NO2
Acquisition Time (sec) 1.0000 Date Sep 28 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.09.28\BM-1372_20180928_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
CH3
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-82.
00
19F NMR spectrum of 3b (376.5 MHz, CD3CN)S17
13 Feb 2019
FW 373.3684 Formula C21H18F3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 17 Oct 2018 23:19:18File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181017\BM-1397d_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
CH3
CH3
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.232.09 0.990.96 0.96
Acetonitrile-d3
7.34
7.24 7.22 7.17
7.15
7.00
6.98
6.90
6.85
6.35
6.33 5.
935.
615.
605.
47
2.27
2.24
7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)
0
0.05
0.10
Inte
nsity
2.092.09 1.06 1.00 0.99 0.990.96 0.960.95 0.86
5.47
5.60
5.61
5.93
6.086.096.10
6.11
6.336.35
6.83
6.85
6.886.
906.
92
6.98
7.00
7.15
7.17
7.22
7.24
7.34
1H NMR spectrum of 3c (400.1 MHz, CD3CN)
S18
13 Feb 2019
FW 373.3684 Formula C21H18F3NO2
Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1397d-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN O
FF
F
H
CH3
CH3
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-81.
95
19F NMR spectrum of 3c (376.5 MHz, CD3CN)
S19
13 Feb 2019
FW 401.4215 Formula C23H22F3NO2
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 02 Oct 2018 15:32:08File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1377-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN O
FF
F
H
CH3
CH3
CH3
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
9.584.27 1.94 0.950.940.94
Acetonitrile-d3
7.50 7.48
7.45
7.25
7.23
7.01
6.98
6.89 6.86
6.84
6.33
6.31
6.11 5.
985.
635.
62
1.31
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
4.27 1.941.05 0.98 0.950.94 0.940.94 0.81
5.515.
625.
63
5.98
6.08
6.10
6.11
6.126.316.33
6.836.
846.86
6.88
6.89
6.906.
987.
01
7.23
7.23
7.25
7.25
7.427.
437.
447.
457.
467.
48
1H NMR spectrum of 3d (400.1 MHz, CD3CN)
S20
13 Feb 2019
FW 401.4215 Formula C23H22F3NO2
Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1377-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN O
FF
F
H
CH3
CH3
CH3
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-81.
97
19F NMR spectrum of 3d (376.5 MHz, CD3CN)
S21
13 Feb 2019
FW 375.3412 Formula C20H16F3NO3
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 29 Sep 2018 14:08:28File Name C:\DOCS\OUTPUT_301\2018\09.ñåí òÿáðü\BM-1373.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN O
FF
F
H
OCH3
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.012.242.09 0.990.97
Acetonitrile-d37.47 7.45
7.00
6.97
6.94
6.92
6.86 6.84
6.36
6.34 5.
925.
635.
58
3.79
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
2.242.09 1.851.011.00 0.990.97 0.960.95 0.71
5.58
5.62
5.63
5.92
6.08
6.096.10
6.12
6.346.36
6.83
6.83
6.84
6.85
6.86
6.89
6.90
6.92
6.94
6.95
6.97
7.00
7.22
7.23
7.24
7.25
7.45
7.47
1H NMR spectrum of 3e (400.1 MHz, CD3CN)
S22
13 Feb 2019
FW 375.3412 Formula C20H16F3NO3
Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM-1373_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000
OHN O
FF
F
H
OCH3
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-82.
02
19F NMR spectrum of 3e (376.5 MHz, CD3CN)
S23
13 Feb 2019
FW 391.4078 Formula C20H16F3NO2S
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 02 Oct 2018 15:34:56File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1378.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN O
FF
F
H
SCH3
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.203.02 2.00 0.95 0.95
Acetonitrile-d3
7.46 7.44 7.
267.
247.
006.
986.
926.
87 6.86
6.34
6.32
6.10
6.09 5.
985.
615.
54
2.47
7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
3.022.00 2.001.00 0.95 0.950.920.91 0.81
5.54
5.60
5.61
5.98
6.08
6.09
6.10
6.116.
326.34
6.84
6.86
6.87
6.906.
926.
946.
987.
00
7.24
7.26
7.44
7.46
1H NMR spectrum of 3f (400.1 MHz, CD3CN)
S24
13 Feb 2019
FW 391.4078 Formula C20H16F3NO2S
Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1378-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN O
FF
F
H
SCH3
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-82.
02
19F NMR spectrum of 3f (376.5 MHz, CD3CN)
S25
13 Feb 2019
FW 379.7600 Formula C19H13ClF3NO2
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 16 Oct 2018 16:12:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1399-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
H
OHN O
FF
F
Cl
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.13 1.99 0.96 0.96
Acetonitrile-d3
7.54
7.52
7.43
7.41
7.26
7.24 7.01
6.98
6.87
6.28
6.03
5.62
5.61
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
2.13 2.06 1.991.06 1.00 0.96 0.960.95 0.91 0.83
5.55
5.615.62
6.03
6.08
6.106.11
6.126.
266.28
6.85
6.87
6.89
6.89
6.916.916.
936.
936.98
7.01
7.24
7.24
7.26
7.26
7.41
7.43
7.52
7.54
1H NMR spectrum of 3g (400.1 MHz, CD3CN)
S26
13 Feb 2019
FW 379.7600 Formula C19H13ClF3NO2
Acquisition Time (sec) 1.9000 Comment STANDARD FLUORINE PARAMETERS Date Oct 1 2018File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM1375_20181001_01\FLUORINE_01 Frequency (MHz) 376.31Nucleus 19F Number of Transients 16 Original Points Count 169643 Points Count 262144Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
H
OHN O
FF
F
Cl
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-81.
95
19F NMR spectrum of 3g (376.5 MHz, CD3CN)
S27
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 16 Oct 2018 20:47:00File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181016\BM-1398-2_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
H
OHN O
FF
F
Br
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
2.12 2.05 0.99 0.98
Acetonitrile-d3
7.58
7.56
7.46
7.44
7.24 7.01 6.98
6.87
6.28
6.04
5.61
5.60
5.56
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
2.12 2.052.03 1.02 0.99 0.980.97 0.960.95 0.87
5.565.
605.
61
6.04
6.08
6.096.11
6.126.
266.28
6.85
6.87
6.89
6.91
6.91
6.95
6.98
7.01
7.24
7.24
7.26
7.44
7.46
7.56
7.58
1H NMR spectrum of 3h (400.1 MHz, CD3CN)
S28
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 1.9000 Date Oct 1 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.01\BM1376_20181001_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 169643Points Count 262144 Pulse Sequence s2pul Solvent DMSO-D6 Sweep Width (Hz) 89285.71Temperature (degree C) 22.000
H
OHN O
FF
F
Br
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-81.
90
19F NMR spectrum of 3h (376.5 MHz, CD3CN)
S29
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Mar 2019 15:56:38File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1520-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
Cl
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Inte
nsity
2.20 1.03 1.000.98
Acetonitrile-d3
7.53
7.51
7.41 7.41
7.35
7.22
6.94
6.84
6.82 6.
105.
945.
715.
53
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
2.202.05 1.05 1.03 1.02 1.000.99 0.98 0.94 0.93 0.80
5.53
5.71
5.72
5.94
6.07
6.096.
106.
11
6.356.37
6.82
6.83
6.84
6.86
6.90
6.92
6.94
6.96
6.997.
227.
24
7.33
7.33
7.35
7.35
7.37
7.41
7.41
7.42
7.43
7.507.51
7.53
1H NMR spectrum of 3i (400.1 MHz, CD3CN)
S30
4 Apr 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 16 Mar 2019 14:04:18File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1520.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 106 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
OHN O
FF
F
H
Cl
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Acetonitrile-d3
Acetonitrile-d314
5.02 13
7.38
134.
4313
2.98
131.
79
129.
0512
8.62
122.
1412
1.87 12
1.62
119.
0511
6.02
93.2
292
.89
92.5
692
.24
78.8
0
144 142 140 138 136 134 132 130 128 126 124 122 120 118 116Chemical Shift (ppm)
0.25
0.50
0.75
1.00
Inte
nsity
Acetonitrile-d3
116.
0211
6.43
119.
0511
9.3112
1.62
121.
8712
2.14
124.
98
127.
81
128.
6212
9.05
129.
9113
0.19
131.
53131.
7713
1.79
132.
98
134.
43
137.
38
145.
02
93.0 92.5 92.0Chemical Shift (ppm)
0.05
0.10
Inte
nsity
92.2
4
92.5
6
92.8
9
93.2
2
13C NMR spectrum of 3i (100.6 MHz, CD3CN)
S31
4 Apr 2019
Acquisition Time (sec) 2.3069 Date Mar 14 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.14\BM-1511-A-F_20190314_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
Cl
OHN O
FF
F
H
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-81.
77
19F NMR spectrum of 3i (376.5 MHz, CD3CN)
S32
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Mar 2019 16:02:18File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1521-2.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
O
O
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Inte
nsity
4.324.01 0.96 0.93 0.68
Acetonitrile-d3
7.23 7.22
7.03
7.01
6.88 6.86
6.84 6.
376.
355.
895.
595.
585.
34 4.27
4.25 4.
234.
23
7.0 6.5 6.0 5.5 5.0 4.5Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
4.324.01 2.001.02 0.96 0.95 0.93 0.92 0.68
4.214.
224.
224.
234.
234.23
4.25
4.25
4.26
4.26
4.26
4.27
5.34
5.58
5.59
5.89
6.06
6.07
6.09
6.106.
356.37
6.84
6.84
6.86
6.88
6.92
6.97
6.99
7.01
7.03
7.037.
227.
237.
247.
25
1H NMR spectrum of 3j (400.1 MHz, CD3CN)
S33
4 Apr 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 16 Mar 2019 21:35:50File Name C:\DOCS\BM\190316\BM-1521_002001r Frequency (MHz) 100.61 Nucleus 13C Number of Transients 128Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30 Solvent CHLOROFORM-DSweep Width (Hz) 24154.59 Temperature (degree C) 27.000
OHN O
FF
F
H
O
O
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Acetonitrile-d3 Acetonitrile-d314
7.96
146.
1514
4.92
138.
33
130.
3812
9.48
128.
8212
8.70
122.
4512
1.39
120.
3311
9.23 11
8.61
118.
0011
5.95
111.
23
93.4
493
.11
92.7
892
.46 78
.29
65.2
665
.05
148 146 144 142 140 138 136 134 132 130 128 126 124 122 120 118 116 114 112Chemical Shift (ppm)
0.25
0.50
0.75
1.00
Inte
nsity
Acetonitrile-d3
111.
23
115.
95
118.
0011
8.61
119.
23
120.
33
121.
3912
2.1212
2.45
124.
96
127.
58
128.
7012
8.82
129.
48
130.
38138.
33
144.
92
146.
15
147.
96
93.5 93.0 92.5Chemical Shift (ppm)
0.05
0.10
Inte
nsity
92.4
6
92.7
8
93.1
1
93.4
4
13C NMR spectrum of 3j (100.6 MHz, CD3CN)
S34
4 Apr 2019
Acquisition Time (sec) 0.7340 Date Mar 19 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.19\bm1521-2-f_20190319_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 1000 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
O
O
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-82.
20
19F NMR spectrum of 3j (376.5 MHz, CD3CN)
S35
4 Apr 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 12 Mar 2019 14:47:30File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1512-P.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
Cl
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
3.04 1.001.00 0.98
Acetonitrile-d3
7.55
7.45
7.43
7.23 7.
217.
00 6.98
6.29
6.07
5.67 5.
49
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
3.042.09 1.03 1.001.00 1.00 0.980.980.97 0.93
5.49
5.665.67
6.07
6.12
6.136.14
6.16
6.28
6.29
6.84
6.856.
866.
876.98
7.00
7.21
7.23
7.417.
417.
437.45
7.46
7.47
7.49
7.55
7.55
7.57
1H NMR spectrum of 3k (400.1 MHz, CD3CN)
S36
4 Apr 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 12 Mar 2019 15:31:56File Name C:\DOCS\OUTPUT_301\2019\03.ì àðò\BM-1512-P.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 1116 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
OHN O
FF
F
H
Cl
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Acetonitrile-d3
Acetonitrile-d3
148.
02
139.
2313
5.03
131.
1313
0.19
127.
3412
4.91
121.
3611
9.67
118.
2011
7.58
113.
34
93.4
993
.16
92.8
392
.50
78.2
0
135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117Chemical Shift (ppm)
0.25
0.50
0.75
1.00
Inte
nsity
Acetonitrile-d3
117.
58
118.
20
119.
24
119.
67
121.
2612
1.36
122.
07
124.
91
127.
34
127.
74
129.
49
130.
0813
0.19
131.
13
134.
17
135.
03
93.5 93.0 92.5Chemical Shift (ppm)
0.05
0.10
Inte
nsity
92.5
0
92.8
3
93.1
6
93.4
9
13C NMR spectrum of 3k (100.6 MHz, CD3CN)
S37
4 Apr 2019
Acquisition Time (sec) 0.7340 Date Mar 12 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.03.12\bm1512-f_20190312_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 100 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
Cl
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-81.
98
19F NMR spectrum of 3k (376.5 MHz, CD3CN)
S38
13 Feb 2019
FW 379.7600 Formula C19H13ClF3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 18 Oct 2018 22:21:32File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181018\BM-1404_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent Tol Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000
OHN O
FF
F
H
Cl
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.19 2.01 1.02 0.98 0.95
Chloroform-d
7.53
7.51
7.40
7.38
7.16
6.85
6.29
6.09
6.00
5.68
3.69
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
3.192.07 2.01 1.02 1.021.01 0.98 0.98
Chloroform-d
5.665.68
6.00
6.06
6.076.
096.
10
6.276.
29
6.84
6.85
6.87
7.16
7.16
7.367.
377.
387.
407.
417.
417.
427.
447.
447.
507.51
7.53
7.53
1H NMR spectrum of 3l (400.1 MHz, CDCl3)
S39
13 Feb 2019
FW 379.7600 Formula C19H13ClF3NO2
Acquisition Time (sec) 1.0000 Date Oct 19 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.19\BM-1404_20181019_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 32 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
Cl
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
C6F6
-84.
16
19F NMR spectrum of 3l (376.5 MHz, CDCl3)
S40
13 Feb 2019
FW 370.3247 Formula C20H13F3N2O2
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 03 Oct 2018 17:50:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1380.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN O
FF
F
H
N
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.04 1.911.02 1.00 0.99
Acetonitrile-d37.
567.
557.
53 7.43
7.41
7.32 7.29 7.20
7.00
6.98
6.60
6.10
5.72
5.71
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7Chemical Shift (ppm)
0
0.1
0.2
0.3
0.4
0.5
Inte
nsity
3.042.06 1.911.021.02 1.001.00 1.00 0.99
5.71
5.72
5.72
6.10
6.36
6.376.
386.
40
6.586.
60
6.98
7.00
7.02
7.20
7.20
7.22
7.22
7.29
7.32
7.397.
397.
417.
437.
447.
457.
46
7.537.
537.
557.
557.
56
1H NMR spectrum of 3m (400.1 MHz, CD3CN)
S41
13 Feb 2019
FW 370.3247 Formula C20H13F3N2O2
Acquisition Time (sec) 2.3069 Date Oct 4 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.04\BM-1380-F_20181004_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN O
FF
F
H
N
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-82.
17
19F NMR spectrum of 3m (376.5 MHz, CD3CN)
S42
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 17 Oct 2018 23:22:50File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181017\BM-1402-2_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
Br
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
4.34 1.051.02 1.00
Acetonitrile-d3
7.55 7.53 7.
43 7.41
7.41
6.99 6.96
6.94 6.22
6.02
5.64
5.59
7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
4.342.22 1.051.021.02 1.001.000.98 0.88
5.595.
635.64
6.02
6.15
6.166.
176.18
6.196.22
6.94
6.96
6.99
7.00
7.01
7.02
7.39
7.40
7.41
7.41
7.43
7.44
7.44
7.45
7.53
7.53
7.55
7.55
1H NMR spectrum of 3n (400.1 MHz, CD3CN)
S43
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 0.4999 Comment Imported from UXNMR. Date 17 Oct 2018 17:16:02File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1402.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 128 Original Points Count 12076 Points Count 65536Pulse Sequence zgpg30 Solvent DMSO-D6 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
OHN O
FF
F
H
Br
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Acetonitrile-d3
Acetonitrile-d3
148.
17
137.
34 135.
1113
1.86
130.
9813
0.11
127.
2912
4.45
120.
7611
9.73
119.
2511
3.25
113.
03
93.5
193
.18
92.8
592
.53
78.1
7
137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)
0.25
0.50
0.75
1.00
Inte
nsity
Acetonitrile-d3
113.
0311
3.25
119.
25
119.
73
120.
76
122.
08124.
45
124.
91
127.
2912
7.75
129.
29
130.
11
130.
9813
1.00
131.
86
135.
11
137.
34
93.5 93.0 92.5Chemical Shift (ppm)
0.025
0.050
Inte
nsity
92.5
3
92.8
5
93.1
8
93.5
1
13C NMR spectrum of 3n (100.6 MHz, CD3CN)
S44
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1402-2-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN O
FF
F
H
Br
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-82.
06
19F NMR spectrum of 3n (376.5 MHz, CD3CN)
S45
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 04 Oct 2018 08:19:12File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1381.H\BM-1381.H_001000fid Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 16384 Points Count 16384Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN O
FF
F
H
Br
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
4.07 1.061.011.00
Acetonitrile-d37.
557.
53 7.41
7.39
7.38
7.36
7.11 7.
096.
796.
776.
75
6.34
6.25
6.08
5.64
5.61
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
4.072.10 1.061.011.00 1.00 0.990.98 0.86
5.61
5.64
5.65
6.08
6.23
6.246.25
6.27
6.326.
34
6.75
6.77
6.79
7.09
7.117.36
7.38
7.39
7.41
7.44
7.45
7.53
7.55
1H NMR spectrum of 3o (400.1 MHz, CD3CN)
S46
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 1.0000 Date Oct 5 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.05\BM-1381_20181005_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 32 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
Br
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-82.
06
19F NMR spectrum of 3o (376.5 MHz, CD3CN)
S47
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Oct 2018 22:02:24File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181027-2\BM-1392-2f_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 8 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
OHN O
FF
F
H
Br
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
4.02 2.00 1.731.02
Acetonitrile-d3
7.56
7.43
7.38
7.23 7.
226.
956.
886.
866.
336.
06 5.74
5.67
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5 5.4 5.3 5.2Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
4.02 2.001.99 1.731.02 1.021.00
5.67
5.74
6.06
6.316.33
6.86
6.86
6.88
6.88
6.90
6.90
6.926.93
6.94
6.95
6.96
7.22
7.22
7.23
7.24
7.38
7.41
7.43
7.44
7.44
7.46
7.48
7.557.56
7.57
7.58
1H NMR spectrum of 3p (400.1 MHz, CD3CN)
S48
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 27 Oct 2018 22:12:02File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\bm181027-2\BM-1392-2f_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 240 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 24154.59Temperature (degree C) 27.000
OHN O
FF
F
H
Br
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Acetonitrile-d3Acetonitrile-d3
147.
96
136.
8613
5.13
132.
6313
0.07
127.
3712
4.78
121.
9711
9.11
118.
04
112.
9911
2.42
93.8
793
.54
93.2
192
.88
83.2
5
137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)
0.25
0.50
0.75
1.00
Inte
nsity
Acetonitrile-d3
112.
42
112.
99118.
04
119.
11
121.
9712
2.13
124.
78
127.
3712
7.62
128.
42
129.
9713
0.07
131.
06
132.
63
135.
13
136.
86
94.0 93.5 93.0 92.5Chemical Shift (ppm)
0.025
0.050
Inte
nsity
92.8
8
93.2
1
93.5
4
93.8
7
13C NMR spectrum of 3p (100.6 MHz, CD3CN)
S49
13 Feb 2019
FW 424.2113 Formula C19H13BrF3NO2
Acquisition Time (sec) 2.0000 Date Oct 29 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.29\BM-1392-2f_20181029_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 89285.71 Temperature (degree C) 22.000
OHN O
FF
F
H
Br
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
C6F6
-81.
95
19F NMR spectrum of 3p (376.5 MHz, CD3CN)
S50
13 Feb 2019
FW 346.3033 Formula C18H13F3N2O2
Acquisition Time (sec) 2.5559 Comment Imported from UXNMR. Date 17 Oct 2018 17:28:12File Name C:\DOCS\OUTPUT_301\2018\10.î êòÿáðü\BM-1394.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 6 Original Points Count 16384 Points Count 65536Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 6410.26Temperature (degree C) 27.000
OHN N O
FF
F
H
14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.141.02 1.011.00
Acetonitrile-d3
7.73
7.72 7.54
7.48 7.46
7.46
7.35
7.34
7.33
7.01 6.99
6.83 6.82 6.82
6.17
5.96
5.81 5.80
7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
3.142.181.131.02 1.01 1.001.000.99 0.97
5.80
5.81
5.96
6.14
6.156.17
6.186.
806.82
6.82
6.83
6.99
7.01
7.327.
337.
347.
357.
367.
37
7.46
7.46
7.48
7.48
7.54
7.557.567.72
7.727.73
6.0 5.5 5.0Chemical Shift (ppm)
0
0.025
0.050
Inte
nsity
1.01 1.000.97 0.51
5.80
5.81
5.96
6.14
6.15
6.17
6.18
1H NMR spectrum of 3q (400.1 MHz, CD3CN)
S51
13 Feb 2019
FW 346.3033 Formula C18H13F3N2O2
Acquisition Time (sec) 2.3069 Date Oct 18 2018 File Name C:\DOCS\OUTPUT_301\F19\2018.10.18\BM-1394-F_20181018_01\FLUORINE_01Frequency (MHz) 376.32 Nucleus 19F Number of Transients 8 Original Points Count 262144Points Count 262144 Pulse Sequence s2pul Solvent ACETONITRILE-D3Sweep Width (Hz) 113636.37 Temperature (degree C) 22.000
OHN N O
FF
F
H
100 80 60 40 20 0 -20 -40 -60 -80 -100 -120 -140 -160 -180 -200Chemical Shift (ppm)
C6F6
-82.
04
19F NMR spectrum of 3q (376.5 MHz, CD3CN)
S52
26 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 06 Jun 2019 19:17:06File Name I:\SPEC_2019_H,C\06.èþ í ü\BM-1604-a_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000
OHN O
FF
F
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.11 3.00 0.97 0.82
Chloroform-d
3.24
5.62
5.635.
685.
976.
846.
946.
977.17
7.19
7.36
7.37
7.39
7.52
7.54
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
3.11 3.002.07 1.01 0.970.94 0.84 0.78 0.150.12
Chloroform-d
5.62
5.635.
68
5.97
6.03
6.04
6.05
6.07
6.08
6.10
6.116.
326.
34
6.816.
836.84
6.86
6.88
6.926.
946.
977.17
7.19
7.357.36
7.377.
397.
397.
407.
417.
427.
437.
527.52
7.54
1H NMR spectrum of diastereomeric mixture of 3a and 3a’ (400.1 MHz, CDCl3)
S53
26 Aug 2019
Acquisition Time (sec) 1.0000 Date Jun 7 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.06.07\BM-1604-a_20190607_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000
OHN O
FF
F
0 -8 -16 -24 -32 -40 -48 -56 -64 -72 -80 -88 -96 -104 -112 -120 -128 -136 -144 -152 -160 -168 -176 -184Chemical Shift (ppm)
87.16
C6F6
-81.
09-8
4.28
19F NMR spectrum of diastereomeric mixture of 3a and 3a’ (376.5 MHz, CDCl3)S54
26 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 31 May 2019 15:12:08File Name C:\DOCS\OUTPUT_301\2019\05.ì àé\BM-1588.H_001001r Frequency (MHz) 400.13 Nucleus 1HNumber of Transients 4 Original Points Count 32768 Points Count 131072 Pulse Sequence zg30Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000
ON O
FF
F
CH3
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
2.93 1.971.95 1.310.94 0.90
3a
3a
3aEthanol
Acetonitrile-d3
Ethanol
7.56 7.
557.
437.
417.
02 7.00 6.
876.
856.
83
6.33
6.07
6.04
5.69
5.68
5.57 3.91 3.
883.
873.
853.
823.
80 3.58
3.56
3.54
1.95
1.94
1.93
1.26
1.24
1.22
1.14
1.12
7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
2.932.00 1.951.00 0.940.91 0.900.66 0.630.24 0.18 0.14
3a
3a
3a
7.56 7.
557.
547.
47
7.46
7.45 7.
447.
437.
437.
417.
397.
397.
387.
27 7.26 7.
257.
25
7.02 7.00
6.91
6.90 6.89 6.88
6.87
6.87
6.85
6.84
6.83
6.33
6.31
6.21 6.20
6.19
6.17
6.14
6.13
6.10
6.07
6.04
5.69 5.68
5.57
1H NMR spectrum of 4 (400.1 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.
S55
26 Aug 2019
Acquisition Time (sec) 1.0000 Date Jun 3 2019 File Name I:\SPEC_F_2019\2019.06.03\BM-1588_20190603_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000
ON O
FF
F
CH3
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200Chemical Shift (ppm)
3a
C6F6
-80.
10-8
1.93
19F NMR spectrum of 4 (376.5 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.
S56
26 Aug 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 31 May 2019 15:20:20File Name C:\DOCS\OUTPUT_301\2019\05.ì àé\BM-1588.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 161 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
ON O
FF
F
CH3
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
3a
3a
3a
3a
3a
3a
3a
3a
3a EtOHEtOH
Acetonitrile-d315
0.50
138.
0813
5.36
131.
0513
0.11
127.
4212
7.36 12
1.57
118.
9611
7.91
112.
78
96.0
695
.74
95.4
395
.11
80.2
7
60.0
3 15.8
1
1.92
1.71
1.51
1.30
1.09
0.68
138 137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118Chemical Shift (ppm)
3a
3a
3a
3a
3a
3a3a
3a
138.
08
135.
36
131.
05
130.
4313
0.11
129.
60 128.
91
127.
5012
7.42
127.
36
124.
66
121.
8212
1.57
118.
96
117.
91
13C NMR spectrum of 4 (100.6 MHz, CD3CN). Signals of 3a are the result of hydrolysis of 4 during preparation and storing of the NMR sample.
S57
27 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 05 Jun 2019 17:26:50File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
4.30 2.561.000.98 0.85
Chloroform-d
(MeCO2CH2S)2
(MeCO2CH2S)2
8.88
8.88
8.13 8.10
8.08
7.70 7.
687.
517.
417.
407.
38 7.23 6.
576.
42
3.78
3.71
3.52
3.31
7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5Chemical Shift (ppm)
4.30 2.562.16 1.781.200.85 0.14
Chloroform-d
(MeCO2CH2S)2
(MeCO2CH2S)2
7.42
7.41
7.41
7.40
7.38
7.36 7.23
7.23
7.22 6.
57
6.42
3.78
3.73
3.71
3.69 3.
633.
553.
52
3.31
N
S
OO
CH3
O
F
F
F
S
OO
CH3
O
F
F
F
1H NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (400.1 MHz, CDCl3). The region with signals of compound 5 are highlighted.
S58
27 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 05 Jun 2019 17:26:50File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent ACETONITRILE-D3 Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
8.9 8.8 8.7 8.6 8.5 8.4 8.3 8.2 8.1 8.0 7.9 7.8 7.7 7.6 7.5 7.4Chemical Shift (ppm)
1.08 1.071.00 1.000.990.98 0.95
8.89 8.88
8.88
8.87
8.15 8.13
8.10 8.
08
7.79
7.78 7.77
7.70
7.68
7.68
7.68 7.
667.
66
7.53
7.51
7.49
7.49
7.42
7.41
7.41
7.40 7.
407.
387.
37 7.36
7.35
7.34
N S
OO
CH3
O
F
F
F
1H NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (400.1 MHz, CDCl3). The region with signals of quinoline are highlighted.
S59
27 Aug 2019
Acquisition Time (sec) 1.0000 Date Jun 3 2019 File Name I:\SPEC_F_2019\2019.06.03\BM-1591_20190603_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 8 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 21.000
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
85.00
C6F6
-78.
72-7
9.60
-78.5 -78.6 -78.7 -78.8 -78.9 -79.0 -79.1 -79.2 -79.3 -79.4 -79.5 -79.6 -79.7Chemical Shift (ppm)
85.00 14.90
-78.
72
-79.
60
N S
OO
CH3
O
F
F
F
19F NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (376.5 MHz, CDCl3)
S60
27 Aug 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 05 Jun 2019 17:41:04File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 361 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
177.
8617
7.51
177.
1617
6.82
171.
2516
8.32
136.
68
130.
2312
9.93
128.
8012
7.58
120.
9611
7.52
114.
8111
4.63
111.
7410
9.26
77.3
277
.00
76.6
8
52.9
052
.53 34
.98
136 134 132 130 128 126 124 122 120 118 116 114 112 110Chemical Shift (ppm)
136.
68
130.
2312
9.93
128.
8012
8.37
127.
8912
7.58
120.
96
120.
41
117.
52
114.
8111
4.63
111.
74
109.
26
N S
OO
CH3
O
F
F
F
178 176 174 172 170 168Chemical Shift (ppm)
0.1
0.2Inte
nsity
168.
32
171.
25
176.
8217
7.16
177.
5117
7.86
13C NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (100.6 MHz, CDCl3). The signals of compound 5 are highlighted.
S61
27 Aug 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 05 Jun 2019 17:41:04File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1591-a.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 361 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
150 148 146 144 142 140 138 136 134 132 130 128 126 124 122Chemical Shift (ppm)
149.
98
147.
67
136.
34
129.
52
128.
89
128.
1612
7.70
126.
55
120.
96
N S
OO
CH3
O
F
F
F
13C NMR spectrum of mixture of quinoline and methyl 2-((4,4,4-trifluoro-3-oxo-1-phenylbut-1-en-1-yl)thio)acetate 5 (100.6 MHz, CDCl3). The signals of quinoline are highlighted.
S62
26 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 20 Jun 2019 19:27:10File Name C:\Users\BM-1\Downloads\BM-1607\BM-1607_001001r Frequency (MHz) 400.13 Nucleus 1HNumber of Transients 8 Original Points Count 32768 Points Count 131072 Pulse Sequence zg30Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000
N
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
3.042.84
Chloroform-d
8.23 8.
218.
178.
157.
887.
827.
547.
537.
517.
48 7.46
7.44
8.30 8.25 8.20 8.15 8.10 8.05 8.00 7.95 7.90 7.85 7.80 7.75 7.70 7.65 7.60 7.55 7.50 7.45Chemical Shift (ppm)
3.042.84 1.121.051.00 1.00 1.00
8.23 8.
21
8.19
8.17
8.17
8.15
7.88
7.86
7.84 7.
82
7.75
7.74
7.72
7.71
7.70
7.54
7.54
7.53
7.52
7.51
7.48
7.48 7.
46
7.44
1H NMR spectrum of 6 (400.1 MHz, CDCl3).
S63
26 Aug 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 01 Jun 2019 14:15:34File Name C:\DOCS\OUTPUT_301\2019\06.èþ í ü\BM-1595.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 146 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent ACETONITRILE-D3 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
N
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
118.
96
126.
2212
7.52
128.
7912
9.61
136.
7413
9.60
148.
19
157.
30
129.5 129.0 128.5 128.0 127.5 127.0Chemical Shift (ppm)
127.
11
127.
41
127.
52
128.
79
129.
26
129.
6112
9.63
13C NMR spectrum of 6 (100.6 MHz, CDCl3)
S64
26 Aug 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 08 Jul 2019 15:50:32File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\BM-1623-1.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent DMSO-D6 Sweep Width (Hz) 8012.82 Temperature (degree C) 27.000
N
O
FF
F
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
3.151.041.00
Chloroform-d
7.25
7.49
7.50
7.57
7.67
7.69
7.968.20
8.23
8.59
8.60 8.55 8.50 8.45 8.40 8.35 8.30 8.25 8.20 8.15 8.10 8.05 8.00 7.95 7.90 7.85 7.80 7.75 7.70 7.65 7.60 7.55 7.50 7.45 7.40Chemical Shift (ppm)
3.152.011.04 1.031.011.00 0.99
7.48
7.49
7.50
7.51
7.52
7.577.
577.
58
7.59
7.65
7.65
7.67
7.69
7.69
7.887.88
7.90
7.91
7.92
7.96
7.988.
208.
23
8.59
1H NMR spectrum of 7 (400.1 MHz, CDCl3)
S65
26 Aug 2019
Acquisition Time (sec) 0.7340 Date Jul 5 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.07.05\BM-1623-R_20190705_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 65536Points Count 65536 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 25.000
N
O
FF
F
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
C6F6
-73.
72
19F NMR spectrum of 7 (376.5 MHz CDCl3)
S66
26 Aug 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 08 Jul 2019 16:10:16File Name C:\DOCS\OUTPUT_301\2019\07.èþ ëü\BM-1623-1.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 505 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent DMSO-D6 Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
N
O
FF
F
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
111.
5411
4.45
117.
3512
0.2612
4.94
125.
9112
7.94
128.
79
132.
9813
8.98
139.
0113
9.33
148.
73
157.
71
184.
0318
4.38
184.
7418
5.10
139 138 137 136 135 134 133 132 131 130 129 128 127 126 125Chemical Shift (ppm)
124.
94
125.
91
127.
94
128.
7212
8.79
128.
90
129.
34
129.
72
132.
98
138.
96138.
9813
9.01
139.
0313
9.33
120 118 116 114 112Chemical Shift (ppm)
0
0.05
Inte
nsity
120.
26 117.
35
114.
45
111.
54
185.0 184.5 184.0Chemical Shift (ppm)
0
0.025
Inte
nsity
185.
10
184.
74
184.
38
184.
03
13C NMR spectrum of 7 (100.6 MHz, CDCl3)
S67
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f1 (мд)
1H.1.fid
3.11
2.10
1.05
1.02
2.05
1.00
0.07
1.94
1.95
2.19
7.50
7.50
7.51
7.52
7.56
7.57
7.58
7.68
7.70
7.72
7.91
7.93
7.95
8.08
8.10
8.12
8.78
7.57.67.77.87.98.08.18.28.38.48.58.68.78.88.9f1 (мд)
3.11
2.10
1.05
1.02
2.05
1.00
7.50
7.50
7.51
7.52
7.56
7.57
7.58
7.68
7.70
7.72
7.91
7.93
7.95
8.08
8.10
8.12
8.78
1H NMR spectrum of 7 (400.1 MHz, CD3CN)
S68
-100-95-90-85-80-75-70-65-60-55-50-45-40-35-30-25-20-15-10-50f1 (мд)
19F_.1.fidF19 -7
2.47
19F NMR spectrum of 7 (376.5 MHz, CD3CN)
S69
0102030405060708090100110120130140150160170180190200f1 (мд)
13C_.1.fid
0.70
0.91
1.11
1.32
1.53
1.73
1.94
112.
7411
5.64
118.
2411
8.54
121.
4412
5.98
126.
4212
9.08
129.
5612
9.82
130.
0713
0.16
130.
1913
0.25
134.
2614
0.67
140.
6914
0.77
149.
64
158.
39
184.
9218
5.27
185.
6318
5.98
112114116118120122124126128130f1 (мд)
112.
74
115.
64
118.
2411
8.54
121.
44
125.
9812
6.42
129.
0812
9.56
129.
8213
0.07
130.
1613
0.19
130.
25
13C NMR spectrum of 7 (100.6 MHz, CD3CN)
S70
3 Oct 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 28 Sep 2019 10:32:32File Name I:\BM-1716-2\BM-1716-2_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000
N O
FF
F
OH
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
7.00 3.56 1.101.00 0.99 0.84 0.38
Chloroform-d
1.76
1.85
1.87
2.06
2.072.
302.332.34
2.37
2.47
2.67
2.692.
71
2.75
2.96
3.02
3.07
3.08
4.104.12
4.14
4.964.97
4.99
5.53
5.61
6.416.44
6.74
6.76
7.01
7.07
7.25
7.38
7.42
7.44
7.1 7.0 6.9 6.8 6.7 6.6 6.5 6.4 6.3 6.2 6.1 6.0 5.9 5.8 5.7 5.6 5.5Chemical Shift (ppm)
3.06 1.00 0.990.830.34 0.330.16
5.53
5.53
5.54
5.57
5.61
6.416.44
6.48
6.636.
646.
646.
666.
666.74
6.74
6.76
6.76
6.78
6.99
7.01
7.037.
077.
08
N OH
FF
F
3.0 2.5 2.0 1.5Chemical Shift (ppm)
0
0.25
0.50
0.75
1.00
Inte
nsity
3.56 1.961.91 1.10 0.730.440.40
3.09 3.08
3.07
3.06 3.
033.
022.
99 2.98
2.97 2.96
2.93 2.79
2.77
2.76
2.75
2.73 2.
712.
69 2.67
2.50
2.50 2.
472.
442.
37 2.34
2.33
2.33 2.
302.
262.
11 2.10 2.10
2.09 2.
07 2.06
2.06
2.05
2.04
1.86 1.85
1.84
1.84
1.76
1.76
1.75
1H NMR spectrum of 8 and 9 (400.1 MHz, CDCl3)
S71
3 Oct 2019
Acquisition Time (sec) 2.0000 Date Sep 30 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.30\BM-1716-2_20190930_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
75.0029.26
C6F6
-87.
99
-80.
79
N O
FF
F
OH
N OH
FF
F
19F NMR spectrum of 8 and 9 (376.5 MHz CDCl3)
S72
3 Oct 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 28 Sep 2019 11:10:38File Name I:\BM-1716-2\BM-1716-2_002001r Frequency (MHz) 100.61 Nucleus 13C Number of Transients 904Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30 Solvent CHLOROFORM-DSweep Width (Hz) 24154.59 Temperature (degree C) 27.000
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
21.6
1
25.9
228
.45
29.9
233
.39
42.0
6
54.3
255
.53
67.1
967
.50
67.8
168
.12
79.1
8
93.8
894.2
194
.53
94.8
6
111.
0211
2.87
116.
1511
8.49
122.
7612
3.18
125.
1312
7.38
129.
1412
9.68
139.
9914
2.18
143.
3514
5.83
132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113 112 111 110 109 108Chemical Shift (ppm)
111.
02
112.
87
116.
15
118.
0611
8.49
120.
90
122.
7612
3.18
123.
7412
4.02
125.
1312
5.48
126.
5812
6.82
126.
9712
7.30
127.
3812
7.54
128.
2512
8.49
129.
0312
9.14
129.
68
N O
FF
F
OH
N OH
FF
F
21.7 21.6Chemical Shift (...
0.25
0.50
0.75
1.00
Inte
nsity
21.7
0
21.6
1
13C NMR spectrum of 8 and 9 (100.6 MHz, CDCl3)
S73
3 Oct 2019
Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 16:01:36File Name I:\SPEC_2019_H,C\09.ñåí òÿáðü\BM-1716-2.APT_004001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 49 Original Points Count 32768 Points Count 131072 Pulse Sequence jmodSolvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81 Temperature (degree C) 27.000
145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20Chemical Shift (ppm)
Chloroform-d
21.6221.71
25.93
28.4629.93
33.40
42.07
54.3
555
.54
67.2
067.5
167
.83
68.1
4
79.1
9
93.8994.2194.54
94.87
111.
0311
2.88
116.
16
118.
50
123.18
125.
1312
5.49
126.
9812
7.38
128.
2612
9.14
129.
68
140.00
142.19143.36
145.83
N O
FF
F
OH
N OH
FF
F
13C APT NMR spectrum of 8 and 9 (100.6 MHz, CDCl3)
S74
3 Oct 2019
Acquisition Time (sec) 1.0000 Date Sep 20 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.20\BM-1709-R_20190920_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 8 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
9.60
C6F6
-85.
01-8
4.53
-82.
98-8
1.51
-81.5 -82.0 -82.5 -83.0 -83.5 -84.0 -84.5 -85.0Chemical Shift (ppm)
9.60 1.16 0.750.58
-85.
01-84.
53
-82.
98
-81.
51
N O
FF
F
O
CH3
N O
FF
F
O
CH3
19F NMR monitoring of hydrogenation of 3a in MeOH.Spectrum of the reaction mixture after first 14 h (376.5 MHz CDCl3)
S75
3 Oct 2019
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 28 Sep 2019 16:54:48File Name C:\DOCS\BM\BM-1709-f\BM-1709-f_001001r Frequency (MHz) 400.13 Nucleus 1H Number of Transients 8Original Points Count 32768 Points Count 131072 Pulse Sequence zg30 Solvent CHLOROFORM-DSweep Width (Hz) 8012.82 Temperature (degree C) 27.000
N O
FF
F
OCH3
19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1Chemical Shift (ppm)
5.09 3.10 3.011.99 1.021.000.99
Chloroform-d
1.86
1.871.89
2.642.68
2.692.
722.
732.
772.
773.
52
5.315.
335.
60
6.20
6.22
6.78
6.81
6.82
6.84
7.25
7.31
7.38
7.39
7.45 7.40 7.35 7.30 7.25 7.20 7.15 7.10 7.05 7.00 6.95 6.90 6.85 6.80 6.75Chemical Shift (ppm)
5.09 1.991.07
Chloroform-d
6.78
6.796.
806.81
6.82
6.82
6.847.
097.
097.
107.11
7.25
7.277.27
7.29
7.31
7.31
7.32
7.33
7.35
7.377.38
7.39
1H NMR spectrum of 10 (400.1 MHz, CDCl3)
S76
3 Oct 2019
Acquisition Time (sec) 2.0000 Date Sep 30 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.30\BM-1709-F_20190930_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 16 Original Points Count 178571Points Count 262144 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000
N O
FF
F
OCH3
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
C6F6
-81.
52
19F NMR spectrum of 10 (376.5 MHz CDCl3)
S77
3 Oct 2019
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 30 Sep 2019 15:45:06File Name I:\SPEC_2019_H,C\09.ñåí òÿáðü\BM-1709-F.C_002001r Frequency (MHz) 100.61 Nucleus 13CNumber of Transients 161 Original Points Count 16384 Points Count 131072 Pulse Sequence zgpg30Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59 Temperature (degree C) 27.000
N O
FF
F
OCH3
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
24.6
5
29.4
3
50.8
182.9
9
95.2
795
.57
95.8
996
.20
105.
63
118.
5212
0.19
121.
4512
3.86
126.
76127.
0812
8.64
129.
5513
0.33
134.
6813
8.80
149.
27
132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117Chemical Shift (ppm)
118.
52
120.
19
121.
01
121.
45
123.
86
126.
7212
6.7612
7.08
128.
64
129.
55
130.
33
13C NMR spectrum of 10 (100.6 MHz, CDCl3)
S78
3 Oct 2019
Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 15:49:36File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-F.APT_004001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 33 Original Points Count 32768 Points Count 131072Pulse Sequence jmod Solvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81Temperature (degree C) 27.000
N O
FF
F
O
CH3
150 145 140 135 130 125 120 115 110 105 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25Chemical Shift (ppm)
Chloroform-d
24.6529.43
50.8
1
82.9
9
105.
64120.
1912
1.45
126.
7612
7.08
128.
6412
9.55
130.33
134.68
138.80
149.26
13C APT NMR spectrum of 10 (100.6 MHz, CDCl3)
S79
Acquisition Time (sec) 4.0894 Comment Imported from UXNMR. Date 27 Sep 2019 15:28:36File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-K.H_001001r Frequency (MHz) 400.13Nucleus 1H Number of Transients 4 Original Points Count 32768 Points Count 131072Pulse Sequence zg30 Solvent CHLOROFORM-D Sweep Width (Hz) 8012.82Temperature (degree C) 27.000
CH3
N O
FF
F
O
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 -4Chemical Shift (ppm)
5.00 2.72 1.070.930.910.89 0.87
Chloroform-d
7.41
7.39 7.37
7.35
7.33
7.31
7.04
6.99 6.
736.
406.
38 5.52
4.92
4.90
4.89
4.87
3.29
2.75 2.60 2.
582.
572.
36 2.33
2.29
2.08
7.05 7.00 6.95Chemical Shift (ppm)
0.90 0.89
7.06
7.04
7.01
6.99
6.97
6.7 6.6 6.5 6.4Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
0.890.88
6.386.
40
6.71
6.73
6.75
3.00 2.75 2.50 2.25 2.00Chemical Shift (ppm)
0
0.05
0.10
0.15
0.20
0.25
Inte
nsity
1.07 0.97 0.93 0.920.920.91
2.04
2.072.08
2.08
2.11
2.11
2.12
2.29
2.322.
332.
362.
392.
412.
412.
432.44
2.45
2.45
2.572.
582.
602.
622.
682.
712.
722.752.
752.
762.
78
3.06
3.07
3.093.11
3.13
1H NMR spectrum of 11 (400.1 MHz, CDCl3)
S80
Acquisition Time (sec) 1.0000 Date Sep 27 2019 File Name C:\DOCS\OUTPUT_301\F19\2019.09.27\BM-1709-K_20190927_01\FLUORINE_01Frequency (MHz) 376.31 Nucleus 19F Number of Transients 4 Original Points Count 89286Points Count 131072 Pulse Sequence s2pul Solvent CHLOROFORM-DSweep Width (Hz) 89285.71 Temperature (degree C) 20.000
CH3
N O
FF
F
O
30 20 10 0 -10 -20 -30 -40 -50 -60 -70 -80 -90 -100 -110 -120 -130 -140 -150 -160 -170 -180 -190 -200 -210Chemical Shift (ppm)
C6F6
-83.
05
19F NMR spectrum of 11 (376.5 MHz CDCl3)
S81
Acquisition Time (sec) 0.6783 Comment Imported from UXNMR. Date 27 Sep 2019 15:38:00File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-K.C_002001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 233 Original Points Count 16384 Points Count 131072Pulse Sequence zgpg30 Solvent CHLOROFORM-D Sweep Width (Hz) 24154.59Temperature (degree C) 27.000
CH3
N O
FF
F
O
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
22.2
926
.30
34.6
0
50.4
5
55.8
3
79.0
4
95.3
095
.61
95.9
296
.23
112.
79
118.
3212
1.29
122.
8212
5.15
128.
3012
9.10
142.
3414
3.47
144 142 140 138 136 134 132 130 128 126 124 122 120 118 116 114 112Chemical Shift (ppm)
112.
79
118.
3211
8.42
121.
29
122.
82
124.
16
125.
15
127.
0412
7.35
127.
4712
8.30
129.
10
142.
34
143.
47
13C NMR spectrum of 11 (100.6 MHz, CDCl3)
S82
Acquisition Time (sec) 1.3664 Comment Imported from UXNMR. Date 30 Sep 2019 15:55:04File Name C:\DOCS\OUTPUT_301\2019\09.ñåí òÿáðü\BM-1709-R.APT_004001r Frequency (MHz) 100.61Nucleus 13C Number of Transients 34 Original Points Count 32768 Points Count 131072Pulse Sequence jmod Solvent ACETONITRILE-D3 Sweep Width (Hz) 23980.81Temperature (degree C) 27.000
CH3
N O
FF
F
O
230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10Chemical Shift (ppm)
Chloroform-d
143.49142.36
129.
1012
7.36
125.
15
122.83
118.
33
112.
80
79.0
5
55.8
5
50.4
6
34.62
26.3222.30
129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113Chemical Shift (ppm)
129.
10
128.
30
127.
4712
7.36
125.
15
122.83
118.
33
112.
80
13C APT NMR spectrum of 11 (100.6 MHz, CDCl3)
S83