4-Fluorobenzyl bromide → (4r,7s)-2-(2-Chloro-4-fluoro-phenyl)-1-(4-fluoro-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

Participants

Reaction Conditions

Reaction Steps

A mixture of (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 43; 150 mg, 0.47 mmol), tetrabutylammonium iodide (174 mg, 0.47 mmol) and 4-fluorobenzyl bromide (230 μL, 1.85 mmol) in dimethylformamide (3 mL) was heated at 80° C. overnight. The solvent was evaporated and dichloromethane (50 mL) was added. The solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL), dried (magnesium sulfate), filtered, concentrated, purified by chromatography, eluting with 50-60% ethyl acetate/petroleum ether, and dried under high vacuum for 2 days to give (4R,7S)-2-(2-chloro-4-fluoro-phenyl)-1-(4-fluoro-benzyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (103 mg, 51%) as a light brown solid. APCI(+)-MS (M+H) 429.

Provenance & Evidence