Trifluoroacetic acid → (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

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Reaction Steps

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(3-fluorophenyl)-2-hydroxyethylcarbamate (223 mg, 0.520 mmol) in dichloromethane (4 mL). To this solution was added trifluoroacetic acid (1.014 mL, 13.16 mmol) and the reaction was allowed to stir over night at room temperature. The reaction solvent was then evaporated in vacuo. The crude reaction mixture was then dissolved in 5 mL of 2N ammonia in methanol and stirred for 5 min. The solvent was then evaporated in vacuo and the crude residue was diluted with dry tetrahydrofuran (4 mL) and carbonyldiimidazole (168 mg, 1.039 mmol) was added and the reaction was stirred at room temperature for 1 hr. The reaction solvent was then evaporated in vacuo and the crude solid was purified by silica gel chromatography 10% EtOAc/90% Hexanes to 30% EtOAc/70% Hexanes affording (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (25 mg, 0.070 mmol, 13.55% yield) and (4R,5R)-5-(5-bromo-2-fluoropyridin-3-yl)-4-(3-fluorophenyl)oxazolidin-2-one (17 mg, 0.048 mmol, 9.2% yield) as an inseparable mixture. 1H-NMR (CDCl3, 400 MHz) δ 8.33 (d, J=2.3, 1H), 7.47-7.41 (m, 1H), 7.19-7.11 (m, 3H), 5.64 (s, 1H), 5.36 (d, J=5.0, 1H), 5.00 (d, J=5.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.09 min. Mass=355.09 (MH)+.

Provenance & Evidence