Hydrochloric Acid → (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of optically-enriched tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(2-fluorophenyl)-2-hydroxyethylcarbamate (93 mg, 0.108 mmol) in dichloromethane (2 mL) at room temperature was added hydrogen chloride (4M in dioxane, 2 mL, 8 mmol). The reaction was warmed to 45° C. and held at that temperature for 1 h. The reaction was concentrated. The reaction was concentrated twice more from tetrahydrofuran. The resulting residue was suspended in tetrahydrofuran (2 mL), cooled to 0° C., and treated with diethylisopropylamine (0.038 mL, 0.217 mmol) and carbonyldiimidazole (26.3 mg, 0.162 mmol). After 5 min, the ice bath was removed and stirring continued for 3 h. The reaction was quenched by addition of 2M ammonia in methanol and concentrated. The resulting residue was suspended in dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% EtOAc/Hex) gave 37.8 mg (49%) as a colorless film. HNMR showed that it was a 1:1 mixture of regioisomers. The mixture was used without separation. Mass spec.: 355.0 (MH)+.

Provenance & Evidence