(2R)-Oxiran-2-ylmethyl butanoate → [3-[3,5-Difluoro-4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methanol

Participants

Reaction Conditions

Reaction Steps

The 1-(tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazine (14.05 g, 31 mmol) was dissolved in dry THF (150 mL) and then cooled to -78° C. (dry ice/acetone). The reaction was next treated with with n-BuLi (21.6 mL, 35 mmol) dropwise over a 25 minute period. The reaction was allowed to stir at -78° C. for 30 minutes and then (R)-(-)-glycidylbutyrate (4.89 mL, 35 mmol) was added dropwise over 7 minutes. The reaction was maintained at -78° C. for an additional 15 minutes and then the bath was removed, allowing the reaction to slowly warm up to room temperature overnight. The reaction was determined to be complete by TLC (5% MeOH/CHCl3, UV short wave). The reaction mixture was diluted with 500 mL CH2Cl2 and then washed with both H2O (3×300 mL) and brine (300 mL). The aqueous portions were back-extracted with more CH2Cl2 (3×400 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to give a creamy yellow solid. The crude solid was purified by recrystallization from hot EtOAc/hexane to give 11.063 g (85%) of the title compound as a white solid with mp 164°-166° C.

Provenance & Evidence