Bromomethylcyclopropane → (4s,7r)-1-(Cyclopropyl)methyl-7,8,8-trimethyl-2-(2,4-difluoro-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

Participants

Reaction Conditions

Reaction Steps

A mixture of (bromomethyl)cyclopropane (2 mL, 20.6 mmol), (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 414 mg, 1.36 mmol) and tetra-n-butylammonium iodide (0.80 g, 2.2 mmol) in N,N-dimethylformamide (5 mL) was heated in a sealed tube in an oil-bath at 100° C. for 20 h. The reaction mixture was cooled to room temperature and then diluted with dichloromethane (200 mL). The solution was washed with water (5×30 mL), aqueous sodium thiosulfate solution (2×30 mL) and brine (30 mL), then dried (magnesium sulfate), filtered, and evaporated, and the residue was purified on an Isco 120 g column, eluting with 30-100% ethyl acetate/hexanes to give (4S,7R)-1-(cyclopropyl)methyl-7,8,8-trimethyl-2-(2,4-difluoro-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (209 mg, 43%) as an pale yellow gum. APCI-MS (M+H) 359.

Provenance & Evidence