Nikitin and Andryukhova
1287
crude product was purified by column chromatography to
give 2a as a liquid, yield 0.12 g (66%). Method B: to a solu-
tion of freshly sublimed zinc bromide (0.34 g, 1.5 mmol) in
dry THF (2 mL), a 3 M solution of methylmagnesium chlo-
ride (0.4 mL, 1.2 mmol) was added under a nitrogen atmo-
sphere. The mixture was stirred 20 min at room temperature,
cooled to 0°C, and a solution of 1a (0.20 g, 1 mmol) in dry
THF (1 mL) was added. The mixture was stirred 1 h at room
temperature, water (0.2 mL) was added, THF was evapo-
rated, and the residue was mixed with water (5 mL), ex-
tracted with ethyl acetate, and dried (MgSO4). The solvent
was evaporated and crude product was purified by column
chromatography to give 2a as a liquid, yield 0.126 g (70%).
stirred at room temperature 30 min and was quenched with
water (1 mL). The solvents were evaporated, water (15 mL)
was added, the mixture was extracted with ethyl acetate (3 ×
3 mL), the combined organic layers were dried (MgSO4),
the solvent was evaporated, and crude product was purified
by column chromatography to give 2g as a solid, yield 0.28g
(78%), mp 72°C. IR (KBr): 1741, 1672 (C=O), 1293,
1
1179 cm–1. H NMR (CDCl3–TMS) δ: 1.15–1.26 (m, 6H),
1.84 (s, 3H), 1.93 (s, 3H), 3.87 (d, 1H, CH(COOEt), J =
3 Hz), 4.03–4.23 (m, 5H, CH2 + CH-Ph), 4.43 (broad s, 1H),
5.18 (d, 1H, J = 15.7 Hz), 7.22–7.31 (m, 5H, Ph). MS m/z:
359 (M+). Anal. calcd. for C20H25NO5: C 66.83, H 7.01, N
3.90; found: C 67.05, H 7.22, N 3.68.
1
IR (KBr): 1675 (C=O), 1395, 1370, 1227 cm–1. H NMR
1-(tert-Butyl)-3,4-dimethyl-5-bis(ethoxycarbonyl)methyl-1,5-
dihydro-2H-pyrrol-2-one (2e): was obtained from 1a (0.201 g,
1 mmol) as a liquid, yield 0.20 g (80%). IR (KBr): 1738,
(CDCl3–TMS) δ: 1.32 (d, 3H, J = 6.5 Hz), 1.49 (s, 9H), 1.72
(s, 3H), 1.85 (s, 3H, CH3), 3.9 (q, 1H, CH, J = 6.5 Hz). MS
m/z: 182 (M+ + 1). Anal. calcd. for C11H19NO: C 72.88, H
10.56, N 7.73; found: C 73.06, H 10.40, N 8.11.
1
1686 (C=O), 1363, 1112 cm–1. H NMR (CDCl3–TMS) δ:
1.16 (t, 3H, J = 6 Hz), 1.31 (t, 3H, J = 6 Hz), 1.50 (s, 9H)
1.70 (s, 3H), 1.90 (s, 3H), 4.05 (q, 2H, J = 6 Hz), 4.26 (q,
2H, J = 6 Hz), 4.16 (d, 1H, J = 2.6 Hz), 4.72 (d, 1H, J =
2.6 Hz). MS: m/z = 326 (M+ + 1). Anal. calcd. for
C17H27NO5: C 62.75, H 8.36, N 4.30; found: C 62.75, H
8.20, N 4.11.
1-tert-Butyl-1,5-dihydro-3,4-dimethyl-5-phenyl-2H-pyrrol-2-one (2b):
Method A: from 1a (0.201 g, 1 mmol) and 2 M phenyl-
magnesium chloride (0.6 mL, 1.2 mmol) 2b was obtained as
a solid, yield 0.15 g (62%), mp 133°C. Method B: from 1a
(0.201 g, 1 mmol), zinc bromide (0.34 g, 1.5 mmol) and 2 M
phenylmagnesium chloride (0.6 mL, 1.2 mmol) 2b was ob-
tained as a solid, yield 0.16 g (65%), mp 133°C. IR (KBr):
2-Benzyl-3-bis(ethoxycarbonyl)methylisoindolin-1-one (2f):
was obtained from 1b (0.257 g, 1 mmol) as a liquid, yield
0.25 g (82%). IR (KBr): 1741, 1672 (C=O), 1293, 1179 cm–1.
1H NMR (CDCl3–TMS) δ: 0.94 (t, 3H, J = 7 Hz), 1.23 (t,
3H, J = 7 Hz), 3.8–3.95 (m, 2H), 4.08 (d, 1H, J = 3.5 Hz),
4.28 (d, 1H, J = 16 Hz), 4.1–4.25 (m, 2H), 5.05 (d, 1H, J =
3.5 Hz), 5.4 (d, 1H, J = 16 Hz), 7.2–7.35 (m, 5H), 7.45–7.55
(m, 3H), 7.9 (m, 1H, Ar). MS m/z: 381 (M+). Anal. calcd.
for C22H23NO5: C 69.28, H 6.08, N 3.67; found: C 69.49, H
6.20, N 3.51.
1
1656 (C=O), 1366, 1225 cm–1. H NMR (CDCl3–TMS) δ:
1.34 (s, 9H), 1.57 (s, 3H), 1.79 (s, 3H), 4.85 (s, 1H), 7.05–
7.33 (m, 5H). MS m/z: 243 (M+). Anal. calcd. for C16H21NO:
C 78.97, H 8.70, N 5.76; found: C 79.10, H 8.89, N 5.70.
2-Benzyl-3-methylisoindolin-1-one (2c) (2): Method A: from
1b (0.257 g, 1 mmol) and 3 M methylmagnesium chloride
(0.4 mL, 1.2 mmol) 2c was obtained as a liquid, yield 0.13 g
(55%). Method B: from 1b (0.257 g, 1 mmol), zinc bromide
(0.34 g, 1.5 mmol) and 3 M methylmagnesium chloride
(0.4 mL, 1.2 mmol) 2c was obtained as a liquid, yield 0.20 g
2-Ethyl-3-methyleneisoindolin-1-one (5): Method A: to a so-
lution of 3 (0.195 g, 1 mmol) in dry THF (3 mL) at 0°C under
nitrogen atmosphere a 3 M solution of methylylmagnesium
chloride (0.5 mL, 1.5 mmol) was added. The reaction mix-
ture was stirred at room temperature for 0.5 h, water
(0.2 mL) was added, THF was evaporated, and the residue
was mixed with aqueous ammonium chloride (5 mL), ex-
tracted with ethyl acetate, and dried (MgSO4). The solvent
was evaporated and crude 4 was heated in benzene (10 mL)
using a Dean-Stark trap and the product was purified by col-
umn chromatography to give 5 as a liquid, yield 0.125 g
(75%). IR (KBr): 1773, 1710 (C=O), 1645, 1398 cm–1.
1H NMR (CDCl3–TMS) δ: 1.24 (t, 3H, J = 5 Hz), 3.82 (q,
1H, J = 5 Hz), 4.80 (d, 1H, J = 2 Hz), 5.17 (d, 1H, J = 2Hz),
7.4–7.5 (m, 2H), 7.65 (d, 1H, J = 4Hz), 7.80 (d, 1H, J =
4 Hz). MS m/z: 173 (M+).
Method B: to a solution of freshly sublimed zinc bromide
(0.34 g, 1.5 mmol) in dry THF (2 mL), a 3 M solution of
methylmagnesium chloride (0.4 mL, 1.2 mmol) was added
under a nitrogen atmosphere. The mixture was stirred
20 min at room temperature, cooled to 0°C, and a solution
of 3 (0.20 g, 1 mmol) in dry THF (1 mL) was added. The
mixture was stirred 1 h at room temperature, water (0.2 mL)
was added, THF was evaporated, and the residue was mixed
with water (5 mL), extracted with ethyl acetate, and dried
(MgSO4). The solvent was evaporated and the residue was
1
(84%). IR (KBr): 1690 (C=O), 1408, 761 cm–1. H NMR
(CDCl3–TMS) δ: 1.43 (d, 3H, J = 7 Hz), 4.26 (d, 1H, J =
15 Hz), 4.38 (quartet, 1H, J = 7 Hz), 5.34 (d, 1H, J =
15 Hz), 7.3–7.6 (m, 8H, Ar), 7.88 (d, 1H, J = 5 Hz). MS
m/z: 237 (M+).
2-Benzyl-3-phenylisoindolin-1-one (2d): Method A: from 1b
(0.257 g, 1 mmol) and 2 M phenylmagnesium chloride
(0.6 mL, 1.2 mmol) 2d was obtained as a solid, yield 0.22 g
(74%); mp 124°C. Method B: from 1b (0,257 g, 1 mmol),
zinc bromide (0.34 g, 1.5 mmol) and 2 M phenylmagnesium
chloride (0.6 mL, 1.2 mmol) 2d was obtained as a solid,
yield 0.22 g (74%). IR (KBr): 1690 (C=O), 1401, 702 cm–1.
1H NMR (CDCl3–TMS) δ: 3.72 (d, 1H, J = 15 Hz), 5.23 (s,
1H), 5.39 (d, 1H, J = 15 Hz), 7.0–7.5 (m, 13H), 7.93 (d, 1H,
J = 5 Hz). MS m/z: 299 (M+). Anal. calcd. for C21H17NO:
C 84.25, H 5.72, N 4.68; found: C 84.55, H 5.76, N 4.43.
1-Benzyl-5-bis(ethoxycarbonyl)methyl-1,5-dihydro-3,4-
dimethyl-2H-pyrrol-2-one (2g): To a suspension of sodium
hydride (0.044 g 60% dispersion, 1.1 mmol) in dry THF
(2 mL) a solution of diethyl malonate (0.176 g, 1.1 mmol) in
1 mL THF was added dropwise with stirring under nitrogen
at 0°C. After 5 min a solution of 1c (0.235 g, 1 mmol) in dry
THF (1 mL) was added dropwise. The reaction mixture was
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