Methane → HCID 57941417, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 150 mg, 0.49 mmol), tetrabutylammonium iodide (181 mg, 0.49 mmol) and 4-chlorobenzyl bromide (400 mg, 1.95 mmol) in dimethylformamide (3 mL) was heated at 80° C. for 4 days. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with water (2×20 mL), saturated aqueous sodium thiosulfate (20 mL), and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 60-70% ethyl acetate/petroleum ether, and dried under high vacuum overnight to give an off-white solid. This was dissolved in ethanol and the solution was treated with charcoal, then filtered through Celite and evaporated. 1H NMR indicated that there was some tetrabutylammonium iodide present. The residue was dissolved in ethyl acetate (50 mL) and the solution was washed with saturated aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and chromatographed, eluting with 75% ethyl acetate/petroleum ether, to give (4S,7R)-1-(4-chloro-benzyl)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (100 mg, 48%). APCI(+)-MS (M+H) 429.

Provenance & Evidence