Hydrochloric Acid → HCID 57941502, compound

Participants

Reaction Steps

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 349 mg, 1.62 mmol) in 1,2-dichloroethane (9 mL) was added to a cooled (0° C.) solution of triethylamine (320 μL, 2.30 mmol) and N′-(5-fluoro-2-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (348 mg, 1.13 mmol) in 1,2-dichloroethane (6 mL) over a period of 1 min. The reaction mixture was stirred for 10 min at room temperature and then in an oil bath at 50° C. for 1 h. A solution of HCl in dioxane (4 M; 8 mL, 32 mmol) was added and the mixture was heated at reflux for 1 h and then allowed to cool to room temperature. Silica gel was added and the solvent was evaporated. The residue was purified using an ISCO40 g column, eluting with 50-100% ethyl acetate/hexanes and then with 10% methanol/ethyl acetate. Fractions homogeneous for the product were evaporated, and the residue was dissolved in dichloromethane (75 mL), and washed with 1:1 water/saturated aqueous sodium thiosulfate (20 mL) and brine (20 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and dried under high vacuum at 95° C. to give (4S,7R)-2-(5-fluoro-2-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (127 mg, 31%) as a white solid. ES(+)-MS (M+H) 369.

Provenance & Evidence