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

Participants

Reaction Steps

A mixture of (R)-[[3-[3-fluoro-4-(3-methoxy-3-methyl1-azetidinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate (0.680 g, 1.75 mmol) in 2:1 ammonium hydroxide/isopropanol (30 mL) was heated to reflux (dry-ice condenser). TLC analysis (5% methanol/chloroform) after 7 hours revealed mostly starting material. The reaction was continued for an additional 46 hours. After cooling to ambient temperature, TLC indicated that the starting mesylate was essentially consumed. The reaction mixture was transferred to a separatory funnel, along with dichloromethane (100 mL), and washed with water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The crude 5-(atminomethyl)oxazolidinone was dissolved in dry dichloromethane (10 mL), cooled to 0° C. with an ice bath, and treated with pyridine (0.698 g, 0.708 mL, 8.75 mmol) and acetic anhydride (0.357 g, 0.330 mL, 3.50 mmol). The cooling bath was then removed and the reaction mixture stirred at ambient temperature overnight. The reaction mixture was diluted with additional dichloromethane (60 mL) and washed with 5% aqueous hydrochloric acid, saturated aqueous sodium carbonate, water and brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to give a crude gum. Radial chromatography over silica gel, eluting with 1%, 2% and 4% methanol/chloroform afforded, after concentration of appropriate fractions, 0.481 g (78%) of the title oxazolidinone antibacterial agent as a white foamy solid. A lyophilized sample had mp 132°-134° C. and MS(EI) 351 (M+).

Provenance & Evidence