(Bromomethyl)cyclobutane → HCID 69019383, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (bromomethyl)cyclobutane (1.7 mL, 15.1 mmol), (4R,7S)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 393 mg, 1.46 mmol) and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) in N,N-dimethylformamide (7 mL) was heated in an oil-bath at 100° C. for 16 h. Additional quantities of (bromomethyl)cyclobutane (1.7 mL, 8.9 mmol) and tetra-n-butylammonium iodide (400 mg, 1.08 mmol) were added and the mixture was heated in an oil-bath at 135° C. for 6 days. The reaction mixture was allowed to cool and it was then diluted with dichloromethane (75 mL) and water (30 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (2×30 mL). The combined organic layers were washed with water (5×30 mL), sodium thiosulfate solution (30 mL) and brine (30 mL). The organic extract was dried (magnesium sulfate), filtered, evaporated, and the residue purified on an Isco 40 g column, eluting with 15-75% ethyl acetate/hexanes and then held under high vacuum to give (4R,7S)-1-(cyclobutyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (52 mg, 11%) as a yellow gum. ES(+)-MS (M+H) 337.

Provenance & Evidence