Ethyl Acetate → (4R)-4-(3-bromo-4-chlorophenyl)pyrrolidin-2-one

(4R)-4-(3-Amino-4-chlorophenyl)pyrrolidin-2-one (12 g, 57.14 mmol) was added to a mixture of 75 mL of 48% HBr/water and 150 mL of water. The solution was cooled in ice. Sodium nitrite (4.33 g, 62.85 mmol) in 10 mL of water was added dropwise. The resulting mixture was stirred for 10 min. Copper(I) bromide (8.9 g, 62.85 mmol) was dissolved in a mixture of 75 mL of 48% HBr/water and 150 mL of water and added dropwise to the reaction mixture. The mixture was then stirred overnight at room temperature. Ethyl acetate (250 mL) was added to the reaction mixture and stirred for 10 min. The organic layer was separated and the aqueous layer was extracted with 200 mL of ethyl acetate. The combined ethyl acetate layers were washed with water (3 times), brine and then concentrated to give the desired product as a brownish yellow oil, which was purified by silica gel column chromatography eluting with methylene chloride/methanol to provide 7.2 g of the title compound (60% yield). 1H-NMR (400 MHz, CD3OD): δ 7.62-7.63 d, J=2.0 Hz, 1H), 7.45-7.47 (m, 1H), 7.26-7.30 (m, 1H), 3.69-3.79 (m, 2H), 3.33-3.37 (m, 1H) 2.67-2.74 (dd, J=16.4, 8.8 Hz, 1H), 2.40-2.47 (dd, J=16.4, 8.4 Hz, 1H); MS (ESI) m/z 275.89 (M+H)+.

1. temperatureThe solution was cooled in ice
2. additionadded dropwise to the reaction mixture
3. stirringThe mixture was then stirred overnight at room temperature
4. stirringstirred for 10 min
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with 200 mL of ethyl acetate
7. washThe combined ethyl acetate layers were washed with water (3 times), brine
8. concentrationconcentrated

ORD 기록

ord-fb5850c05d604911b10caf694ebca7a3

출처 데이터셋

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08344028B2