Ammonium Chloride → 3-bromo-5-(2-chloro-4-fluorophenyl)-alpha-(2,4-difluorophenyl)-1-methyl-1H-pyrazole-4-methanol

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-bromo-5-(2-chloro-4-fluorophenyl)-4-iodo-1-methyl-1H-pyrazole (i.e. the product of Step D) (250 mg, 0.602 mmol) in tetrahydrofuran (3 mL) at −78° C. was added dropwise n-butyllithium (2.5 M solution in hexanes, 0.36 mL, 0.90 mmol). Stirring was continued for 1 h at −78 to −40° C., and then the reaction mixture was cooled to −78° C. and 2,4-difluorobenzaldehyde (103 mg, 0.72 mmol) in tetrahydrofuran (2 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred for 3 h, and then saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (10 to 50% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as an off-white solid (35 mg).

Provenance & Evidence