反应详情

温度

0 °C

To a solution of 4-benzyl-3-{2-[5-(3,5-difluoro-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoyl}-oxazolidin-2-one (23.40 g, 36.73 mmol) in THF (180 mL) was added water (60 mL). The system was cooled to 0° C. To this cold solution was added LiOH.H2O (1.54 g, 36.73 mmol) and 30% H2O2 (16.65 mL, 146.92 mmol), drop-wise, maintaining the internal temperature below 5° C. The resulting cloudy solution was stirred at 0° C. for 20 min. The excess H2O2 was quenched by adding 1.5 M aqueous Na2SO3 solution (97.9 mL, 146.92 mmol) and stirred at room temperature for 15 min. The organic solvent was removed in vacuo. The resulting liquid was acidified to pH 2 by adding 1 N aqueous HCl solution. The aqueous layer was extracted with EtOAc (3×200 mL), dried over MgSO4, and concentrated in vacuo resulting in a crude mixture which was purified by ISCO silica gel column chromatography to yield (R)-2-[5-(3,5-difluoro-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid (12.25 g, 70%).

1. temperaturemaintaining the internal temperature below 5° C
2. customThe excess H2O2 was quenched
3. stirringstirred at room temperature for 15 min
4. customThe organic solvent was removed in vacuo
5. additionby adding 1 N aqueous HCl solution
6. extractionThe aqueous layer was extracted with EtOAc (3×200 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customresulting in a crude mixture which
10. customwas purified by ISCO silica gel column chromatography