Water → 4-(4,4-difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol

Participants

Reaction Conditions

Reaction Steps

To a solution of 389 mg (0.600 mmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol, which was prepared by a method similar to that of Example 4, in 3 ml of 1-methyl-2-pyrrolidone, 489 mg (1.50 mmol) of cesium carbonate and 344 mg (1.20 mmol) of (S)-(+)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluene sulfonate were added, and the reaction solution was stirred at 70° C. for 2 hours. After completion of the reaction, water and ethyl acetate were poured into the reaction solution and the reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=95/5-50/50 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 400 mg (0.524 mmol) of 4-(4,4-difluorocyclohexyl)-2-[1-(5-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy}pyrimidin-2-yl)piperidin-4-yl]-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-ol as a white solid.

Provenance & Evidence