Hydrochloric Acid → (4R,5R)-4-(5-Bromo-2-fluoropyridin-3-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

To a solution of optically-enriched tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(2,5-difluorophenyl)-2-hydroxyethylcarbamate (380 mg, 0.850 mmol) in dichloromethane (6 mL) at room temperature was added hydrochloric acid (4M in dioxane, 10 mL, 40.0 mmol). The resulting solution was placed in a 45° C. bath. After 20 min, the reaction was concentrated. The resulting viscous oil was dissolved in and reconcentrated from tetrahydrofuran (3×) to give a white solid. The resulting residue was suspended in tetrahydrofuran (15 mL), and treated with diethylisopropylamine (0.297 mL, 1.70 mmol). After stirring briefly, the mixture was cooled to 0° C. and treated with carbonyldiimidazole (207 mg, 1.27 mmol) as a solid in one portion. The ice bath was removed and stirring continued for 1.5 h. The reaction was quenched by addition of 2M ammonia in methanol and concentrated. The material was purified by column chromatography (EtOAc/Hex) to give the product as a mixture of regioisomers. The material was re-purified by chiral prep HPLC (Chiralcel OJ, 30% EtOH/heptane/0.1% DEA) to afford 88 mg (25%). 1H NMR (CDCl3) δ: 8.33 (dd, J=2.3, 1.4 Hz, 1H), 8.11 (dd, J=8.2, 2.1 Hz, 1H), 7.21-7.27 (m, 1H), 7.09-7.17 (m, 2H), 6.48 (br. s., 1H), 5.58 (d, J=5.8 Hz, 1H), 5.04 (d, J=5.5 Hz, 1H). 19F NMR (CDCl3) δ: −74.27 (br. s., 1F), −116.97 (d, J=17.3 Hz, 1F), −123.78-123.41 (m, 1F). Mass spec.: 373.0 (MH)+.

Provenance & Evidence