Dichloromethane → (4s,7r)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1-(3,3,3-trifluoro-propyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

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; 200 mg, 0.66 mmol), tetrabutylammonium iodide (190 mg, 0.51 mmol) and 3-bromo-1,1,1-trifluoropropane (Aldrich; 5.00 g, 28.25 mmol) in dimethylformamide (2 mL) was heated in a pressure tube in an oil-bath at 100° C. for 4 days. An additional portion of tetrabutylammoiun iodide (190 mg, 0.51 mmol) was added and the reaction mixture was heated at 100° C. for 3 days and then cooled to room temperature. Dichloromethane (150 mL) was added and the solution was washed with water (5×25 mL) and aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and purified using an ISCO 40 g column, eluting with 30-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated and the residue was triturated with petroleum ether. The mixture was evaporated again and dried at 70° C. under high vacuum to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-(3,3,3-trifluoro-propyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (46 mg, 17%) as a light yellow solid. ES(+)-MS (M+H) 401.

Provenance & Evidence