反应详情

温度

-78 °C

3-Butenylmagnesium bromide (0.5M in tetrahydrofuran, 75 mL, 37.5 mmol) was added slowly to a stirred, cooled −78° C. solution of (2R,3R,4R)-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1; 11.1 g, 24.9 mmol) in tetrahydrofuran (125 mL). The mixture was stirred at −78° C. for 3 hours, then at room temperature for 1.5 hour. Saturated aqueous ammonium chloride (20 mL) was added slowly, followed by ethyl acetate (300 mL). The layers were separated and the organic layer was washed with brine (100 mL). The combined aqueous layers were extracted with ethyl acetate (100 mL), the combined organic layers were dried (Na2SO4), and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (97:3 increasing to 80:20), to give the title compound (8:1 mixture of alcohol diastereoisomers) as a colorless oil (10 g, 80%).

1. waitat room temperature for 1.5 hour
2. customThe layers were separated
3. washthe organic layer was washed with brine (100 mL)
4. extractionThe combined aqueous layers were extracted with ethyl acetate (100 mL)
5. dry with materialthe combined organic layers were dried (Na2SO4)
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by column chromatography on silica gel
8. washeluting with hexane/EtOAc (97:3 increasing to 80:20)