Ammonium Chloride → 1-Benzyl-3-(2,3-difluorophenyl)pyrrolidin-3-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-2,3-difluorobenzene (5.79 g, 30 mmol) in dry diethyl ether (50 mL) under nitrogen at −78° C., was added dropwise n-butyllithium (2.5 M in hexane, 13.2 mL, 33 mmol). The mixture was stirred for 30 min at −78° C. after which a solution of 1-benzylpyrrolidin-3-one (5.25 g, 30 mmol) in dry diethyl ether (15 mL) was added drop wise. The mixture was stirred at −78° C. for 1 h and at ambient temperature for 1 h. Saturated aqueous ammonium chloride (50 mL) was added and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated. Purification by flash chromatography on silica gel (ethylacetate/isooctane/triethylamine, 10:85:5). Yield: 3.7 g. The enantiomers were separated by HPLC on Kromasil 5-Cellucoat (heptane/2-propanol/diethyl amine, 99:1:0.1): (+)-enantiomer (1.69 g). [α]D=+47.0° (methanol). MS m/z (rel. intensity, 70 eV) 289 (M+, 38), 198 (76), 133 (64), 132 (47), 91 (bp). (−)-enantiomer (1.54 g). [α]D=−46.2° (methanol). MS m/z (rel. intensity, 70 eV) 289 (M+, 11), 198 (43), 133 (56), 132 (40), 91 (bp).

Provenance & Evidence