反应详情

温度

90 °C

(4R)-4-(3-Bromo-4-chlorophenyl)pyrrolidin-2-one (0.5 g, 0.55 mmol) and 3-methoxycarbonylphenyl boronic acid (0.144 g, 0.55 mmol) were mixed with DMF (2 mL). The mixture was degassed by alternately applying a vacuum and flushing with nitrogen. Palladium acetate (0.025 g, 0.11 mmol) and tetrabutylammonium bromide (0.053 g, 0.165 mmol) were added followed by potassium phosphate (0.35 g, 1.65 mmol). The mixture was stirred overnight at 90° C., then cooled to room temperature, diluted with ethyl acetate (30 mL), washed with a 10% aqueous HCl solution then brine, and concentrated in vacuo. The product, 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid, was then treated with HCl as described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride to provide the title compound (25). 1H-NMR (400 MHz, CD3OD): δ8.03-8.06 m, 2H), 7.65-7.68 (m, 2H), 7.55-7.57 (m, 1H), 7.33-7.37 (m, 2H), 3.42-3.49 (m, 1H), 3.2-3.26 (m, 2H), 2.77-2.83 (dd, J=16.8, 6.4 Hz, 1H), 2.63-2.69 (dd, J=16.4, 7.6 Hz, 1H); MS (ESI) m/z 333.98 (M+H)+.

1. customThe mixture was degassed
2. customflushing with nitrogen
3. temperaturecooled to room temperature
4. washwashed with a 10% aqueous HCl solution
5. concentrationbrine, and concentrated in vacuo
6. additionThe product, 3-[5-((3R)-5-oxopyrrolidin-3-yl)-2-chlorophenyl]benzoic acid, was then treated with HCl
7. customas described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride