反应详情

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate (141 mg, 0.328 mmol) in dichloromethane (4 mL). To this solution was added trifluoroacetic acid (0.253 mL, 3.28 mmol) and the reaction was allowed to stir over night at room temperature. The next day the reaction was checked by LC/MS and was complete. 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 (53.3 mg, 0.328 mmol) was added and the reaction was allowed to stir overnight. The reaction was complete by LC/MS. The reaction 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 (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(4-fluorophenyl)oxazolidin-2-one (20 mg, 0.056 mmol, 42.9% yield) and its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=1.79 min. Mass=354.89 (MH)+.

1. customThe reaction solvent was evaporated in vacuo
2. additionthe crude oil was diluted with diethylether
3. washwashed with saturated sodium bicarbonate
4. customThe organic layer was separated
5. dry with materialdried over sodium sulfate
6. customthe solvent was then evaporated in vacuo
7. additionthe crude residue was diluted with dry tetrahydrofuran
8. temperatureThe solution was cooled to 0° C.
9. stirringto stir overnight
10. customThe reaction solvent was then evaporated in vacuo
11. customthe crude solid was purified by silica gel chromatography 15% EtOAc/85% Hexanes to 50% EtOAc/50% Hexanes