Ethyl Acetate → tert-Butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

20% palladium hydroxide (75.8 mg) was added to a solution of tert-butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-1-[(2,6-dichlorophenyl)methyl]-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate obtained in Example 5b (a chiral form corresponding to the peak with a shorter retention time) (758 mg, 1.29 mmol) in methanol (20 ml), followed by stirring at 40° C. for three hours under a hydrogen atmosphere. The reaction liquid was filtered, and the filtrate was concentrated to give a crude product (501 mg). 2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (145 mg, 0.532 mmol) and potassium carbonate (53.2 mg) were added to a solution of this crude product (174 mg) in N,N-dimethylformamide (dehydrated) (6 mL), followed by stirring overnight. 2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (145 mg, 0.532 mmol) and potassium carbonate (106 mg) were further added, followed by stirring for four hours. Ethyl acetate was added to the reaction liquid, which was washed with a 1N aqueous sodium hydroxide solution and brine. This was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to give the title compound (82 mg, yield: 32.4%).

Provenance & Evidence