Methanol → tert-butyl 2-[(3R*,4S*)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate

Participants

Reaction Conditions

Reaction Steps

A mixture of the chiral form of tert-butyl 2-[(3R*,4S*)-1-benzyl-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate obtained in Example 1k (161 mg, 0.32 mmol), 20% palladium hydroxide (135 mg) and methanol (5 ml) was stirred at mom temperature for 15 hours under a hydrogen atmosphere. The atmosphere in the reaction vessel was replaced with nitrogen, 20% palladium hydroxide was filtered off, and the solvent was distilled off. 2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (159 mg, 0.581 mmol), potassium carbonate (97 mg, 0.702 mmol) and N,N-dimethylformamide (2 ml) were added to the resulting residue, which was heated at 45° C. for three hours and 15 minutes. Water was added to the reaction mixture, which was extracted with ethyl acetate twice. The organic layer was washed with a saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane) to give the title compound (153 mg, yield 78.9%).

Provenance & Evidence