Nitrogen → (S)-N-[[3-[3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

Participants

Reaction Steps

A solution of 3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)nitrobenzene (1.60 g, 6.7 mmol) in 25% tetrahydrofuran/methanol (35 mL) was degassed by repeated evacuation and filling with N2 and then treated with 10% palladium/carbon (0.160 g). Ammonium formate (2.10 g, 33.3 mmol) was then added and the mixture degassed a final time. The reaction mixture was stirred at ambient temperature for 20 minutes, during which time the yellow reaction mixture became colorless. TLC analysis (2:1 hexane/ethyl acetate) revealed the reduction to be complete. The reaction mixture was filtered through Celite® (dichloromethane and methanol wash) and the filtrate concentrated in vacuo to give a purple gum that was immediately dissolved in 1:1 acetone/water (30 mL) under N2. The mixture was cooled with an ice bath to 0° C. and treated with sodium bicarbonate (1.10 g, 13.4 mmol) and benzyl chloroformate (1.20 g, 1.00 mL, 7.37 mmol). The cooling bath was allowed to dissipate over a 3 h period. After stirring a further 2 h at ambient temperature, the reaction mixture was transferred to a separatory funnel with dichloromethane (50 mL). The organic phase was separated, washed with water, dried over sodium sulfate, filtered and concentrated in vacuo to give a purple oil. Chromatography over silica gel, eluting with 6:1 hexane/ethyl acetate, afforded, after concentration of appropriate fractions, 2.04 g (89%) of the title compound as a viscous oil which solidified on standing to a waxy solid with mp 73°-75° C. and MS(EI) 344 (M+). Step 4: (R)-[3-[3-fluoro-4-(3-methoxy-3-methyl-1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methanol

Provenance & Evidence