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

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Reaction Conditions

Reaction Steps

A mixture of (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 42; 989 mg, 3.25 mmol), tetrabutylammonium iodide (600 mg, 1.63 mmol) and allyl iodide (1.05 mL, 9.75 mmol) in dimethylformamide (5.7 mL) was heated in an oil-bath at 100° C. overnight. The solvent was evaporated and dichloromethane (400 mL) was added. The solution was washed with aqueous sodium thiosulfate (2×100 mL) and the combined aqueous washes were back-extracted with dichloromethane (2×100 mL). The combined organic layers were washed with water (100 mL) and brine (100 mL), dried (magnesium sulfate), filtered, and purified using an ISCO 40 g column, eluting with 20-50% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated successively with methanol, ether, and petroleum ether. The residue was triturated with hexane and the solid was dried under high vacuum at 70° C. overnight and then at 85° C. for 1 h to give (4R,7S)-1-allyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (334 mg, 30%) as an off-white solid. APCI(+)-MS (M+H) 345.

Provenance & Evidence