(R)-Tert-butyl 3-(3-chlorobenzoyl)piperidine-1-carboxylate → 1,1-Dimethylethyl (3R)-3-[(1S)-1-(3-chlorophenyl)-5,5-difluoro-1-hydroxyhexyl]-1-piperidinecarboxylate

Participants

Reaction Steps

A solution of (3R)-1-(tert-butoxycarbonyl)-3-(3-chlorobenzoyl)piperidine (100 mg, 0.33 mmol) in THF (2 mL) was cooled to −20° C. and 4,4-difluoropentylmagnesium chloride (˜0.79M in THF, 5.0 mL, 4.0 mmol) was added. The mixture was stirred for 2 h and quenched with sat'd NH4Cl. The aqueous layer was extracted with ether. The combined organic layers were washed with brine, dried over sodium sulfate and filtered. The solvent was removed on a roto-evaporator. The crude product was purified using flash chromatography (hexanes/EtOAc). N-Boc-(S)-1-(3-chlorophenyl)-5,5-difluoro-1-((R)-piperidin-3-yl)hexan-1-ol was isolated as an oil (70 mg) MS m/z 454 (M+Na).

Provenance & Evidence