Ammonium Chloride → 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-{1-[5-(1-hydroxy-2-methylpropyl)pyrimidin-2-yl]piperidin-4-yl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline

Participants

Reaction Steps

To a solution of 213 mg (0.273 mmol) of 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-formyl pyrimidin-2-yl)piperidin-4-yl]-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 16, in 5 ml of tetrahydrofuran, 0.5 ml (0.5 mmol) of 1.0 mol/L isopropyl magnesium bromide-tetrahydrofuran solution was added under an argon gas atmosphere, and the reaction solution was stirred at room temperature for 0.5 hour. Then, 0.5 ml (0.5 mmol) of 1.0 mol/L isopropyl magnesium bromide-tetrahydrofuran solution was further added and the reaction solution was stirred at room temperature for 0.5 hour. After completion of the reaction, the reaction solution was poured into saturated ammonium chloride aqueous 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=85/15-80/20 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 174 mg of the title compound as a white solid (yield: 77%).

Provenance & Evidence