反应详情

Allylmagnesium bromide (15.4 mL, 15.4 mmol) was slowly added to a stirred, cooled −40° C. solution of chlorobis[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane (5.91 g, 18 mmol) in diethyl ether (20 mL). The mixture was warmed to room temperature and stirred for 1 hour before cooling to −78° C. (2R,3R,4R)-2-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1; 5.5 g, 12.3 mmol) in diethyl ether (10 mL) was slowly added and the mixture was stirred at −78° C. for 1.5 hours. The mixture was warmed to room temperature and stirred for a further 1.5 hours. The mixture was cooled to −78° C. and aqueous sodium acetate (3M, 20 mL) then aqueous hydrogen peroxide (31% wt, 10 mL) were added. The mixture was allowed to warm to room temperature and stirred overnight. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/hexane (90:10), to give the title compound as a yellow oil (4.7 g, 78%).

1. additionwas slowly added
2. stirringthe mixture was stirred at −78° C. for 1.5 hours
3. temperatureThe mixture was warmed to room temperature
4. stirringstirred for a further 1.5 hours
5. temperatureThe mixture was cooled to −78° C.
6. temperatureto warm to room temperature
7. stirringstirred overnight
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with ethyl acetate (2×150 mL)
10. dry with materialThe combined organic fractions were dried (MgSO4)
11. customthe solvent was evaporated under reduced pressure
12. customThe residue was purified by column chromatography on silica gel
13. washeluting with EtOAc/hexane (90:10)