Methyl iodide → HCID 22933409, compound

Participants

Reaction Conditions

Reaction Steps

A solution of N-[4-methoxy-3-(trifluoromethyl)-phenyl]-2,2-dimethylpropanamide (5.90 g, 21.4 mmol) in tetrahydrofuran (70.0 ml) was cooled to −10 to −15° C., and then a 1.57M n-butyllithium/hexane solution (33.5 ml, 52.5 mmol) was added dropwise thereto over a period of 25 minutes while maintaining the internal temperature at 0° C. or lower. The resulting mixture was slowly warmed up to 20° C. and stirred for 3 hours while maintaining the temperature. The resulting suspension was cooled to −35 to −40° C., and then iodomethane (1.53 ml, 24.6 mmol) was added dropwise thereto over a period of 15 minutes. The resulting mixture was slowly warmed up to −5 to 0° C. and stirred for 1.5 hours while maintaining the temperature. The mixture was partitioned and extracted with water and ethyl acetate, and the organic phase was washed with a 5% aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure to obtain a crude product (6.23 g). The crude product was purified by a silica gel column chromatography (eluent: hexane/diisopropyl ether=1/1) to obtain N-[4-methoxy-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (3.20 g, 50%).

Provenance & Evidence