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 100 mg (0.120 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 0.6 ml of toluene, 21 mg (0.24 mmol) of morpholine, 14 mg (0.048 mmol) of (2-biphenyl)di-tert-butyl phosphine, 23 mg (0.24 mmol) of sodium tert-butoxide and 11 mg (0.012 mmol) of tris(dibenzylidene acetone)dipalladium (0) were added, and the reaction solution was stirred at 60° C. for 50 minutes while microwave irradiating using a microwave reactor (product name: Initiator, manufactured by Biotage). After completion of the reaction, the reaction solution was poured into saturated sodium hydrogencarbonate aqueous solution and 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=80/20-50/50 (V/V)] to provide 89 mg of 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 as an orange solid (yield: 88%).

Provenance & Evidence