Tert-Butyl nitrite → (3R)-4-Amino-3-(3,4-dichlorophenyl)butanoic acid hydrochloride

Temperature

60 °C

Copper(II) chloride (0.183 g, 1.37 mmol) and tert-butyl nitrite (0.2 mL, 1.71 mmol) was stirred in acetonitrile (1 mL) at 0° C. (4R)-4-(3-Amino-4-chlorophenyl)pyrrolidin-2-one (0.24 g, 1.14 mmol) in acetonitrile (1 mL) was added dropwise. The mixture was warmed to 60° C. and stirred for 1 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate, and washed with a 10% aqueous HCl solution, brine, and the ethyl acetate layers were concentrated. Hydrolysis of the resulting lactam with aqueous HCl as described for the preparation of (3R)-4-amino-3-(3-bromo-4-chlorophenyl)butanoic acid hydrochloride provided the title compound. 1H-NMR (400 MHz, CD3OD): δ 7.53-7.54 (m, 1H), 7.51 (s, 1H), 7.26 (m, 1H), 3.28-3.41 (m, 2H), 3.15-3.21 (m, 1H), 2.77-2.83 (dd, J=16.4, 6.4 Hz, 1H) 2.63-2.69 (dd, J=16.8, 8.0 Hz, 1H); MS (ESI) m/z 247.99 (M+H)+.

1. additionwas added dropwise
2. temperatureThe reaction mixture was then cooled to room temperature
3. washwashed with a 10% aqueous HCl solution, brine
4. concentrationthe ethyl acetate layers were concentrated
5. customHydrolysis of the resulting lactam with aqueous HCl

ORD record

ord-a54c253a4e4146118fee59aaac587b72

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344028B2