Trifluoroacetic acid → HCID 69086172, compound

Participants

Reaction Steps

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate (1450 mg, 3.38 mmol) in dichloromethane (12 mL). To this solution was added trifluoroacetic acid (2.60 mL, 33.8 mmol) and the reaction was allowed to stir over night at room temperature. The reaction solvent was evaporated in vacuo and the crude oil was diluted with diethylether and washed with saturated sodium bicarbonate. The organic layer was separated, dried over sodium sulfate and the solvent was then evaporated in vacuo and the crude residue was diluted with dry tetrahydrofuran. The solution was cooled to 0° C. and carbonyldiimidazole (282 mg, 1.74 mmol) was added and the reaction was allowed to stir overnight. The reaction solvent was then evaporated in vacuo and the crude residue was diluted with 2N ammonia in methanol and stirred for 15 min. The solvent was then evaporated in vacuo and the crude solid was purified by silica gel chromatography 15% EtOAc/85% Hexanes to 50% EtOAc/50% Hexanes affording the desired product and its regioisomer as an inseparable mixture. The inseparable mixture was further purified by reverse phase chromatography using a sunfire col 30×100 45%-55% MeOH/H2O 0.1% TFA over a 20 minute run time affording (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(4-fluorophenyl)oxazolidin-2-one (180 mg, 0.507 mmol, 10.99% yield). 1H-NMR (CDCl3, 400 MHz) δ 8.33 (s, 1H), 8.10 (d, J=8.0), 7.42-7.38 (m, 2H), 7.19-7.15 (m, 2H), 5.81 (brs, 1H), 5.36 (d, J=4.0, 1H), 5.01 (d, J=4.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.17 min. Mass=356.96 (MH)+.

Provenance & Evidence