Hydrogen Peroxide → (2R,3R,4R,alphaR)-alpha-2-Propenyl-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanol

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Reaction Steps

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%).

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