4-(Trifluoromethyl)phenyl isocyanate → (4S)-4-hydroxy-3,3-dimethyl-N-[4-(trifluoromethyl)phenyl]-1-pyrrolidinecarboxamide

Participants

Reaction Steps

To 200 mg (1.3 mmol) of (3S)-4,4-dimethyl-3-pyrrolidinol hydrochloride and 0.25 mL (1.3 mmol) of N,N-diisopropylethylamine in 4 mL of dichloromethane was added dropwise 0.19 mL (1.3 mmol) of 1-isocyanato-4-(trifluoromethyl)benzene. The reaction mixture was stirred at room temperature for 18 h. It was then diluted with ethyl acetate, and the resulting solution was washed with 1 N hydrochloric acid and brine, dried over magnesium sulfate, and concentrated under reduced pressure to afford 390 mg (quantitative yield) of (4S)-4-hydroxy-3,3-dimethyl-N-[4-(trifluoromethyl)phenyl]-1-pyrrolidinecarboxamide. 1H NMR (300 MHz, DMSO-d6) δ 8.45 (s, 1H), 7.73 (d, J=9 Hz, 2H), 7.54 (d, J=9 Hz, 2H), 5.08 (s, 1H), 3.74-3.55 (m, 2H), 3.27-3.09 (m, 3H), 0.97 (s, 3H), 0.95 (s, 3H). Cl-LCMS m/z 303 (M+H).

Provenance & Evidence