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

Participants

Reaction Conditions

Reaction Steps

To a solution of 5.09 g (6.12 mmol) of (−)-2-[1-(5-Bromopyrimidin-2-yl)piperidin-4-yl]-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 11, in 50 ml of toluene, 10 ml of tert-butanol, 1.6 ml (18 mmol) of morpholine, 1.73 g (18.0 mmol) of tert-butoxy sodium, 437 mg (0.917 mmol) of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl and 107 mg (0.477 mmol) of palladium acetate were added under an argon gas atmosphere, and the reaction solution was stirred at 110° C. for 2.8 hours. After completion of the reaction, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was 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=8/2-7/3-6/4 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 4.30 g of the title compound as a white solid (yield: 84%).

Provenance & Evidence