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

Participants

Reaction Conditions

Reaction Steps

To a solution of 95.0 mg (0.146 mmol) of (5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-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 Reference Example 23, in 0.4 ml of N,N-dimethylformamide, 92.4 mg (0.322 mmol) of (S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl p-toluenesulfonate and 54.2 mg (0.392 mmol) of potassium carbonate were added, and the mixture was stirred at 90° C. for 5 hours. After completion of the reaction, the reaction solution was poured into water and extracted with toluene twice. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=80/20-59/41 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 91.3 mg of the title compound as a white solid (yield: 82%).

Provenance & Evidence