Hydrochloric Acid → HCID 57941365, compound

Participants

Reaction Steps

Triethylamine (300 μL, 2.15 mmol) was added dropwise to a cooled (0° C.) solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 220 mg, 1.03 mmol) in 1,2-dichloroethane (3 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of N-(2,6-difluoro-phenyl)-N′-methyl-hydrazinecarboxylic acid tert-butyl ester (167 mg, 0.65 mmol) in 1,2-dichloroethane (6 mL) was added over 2 min. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 30 min, and then in an oil bath at 50° C. for 1 h. The solution was allowed to cool and a solution of HCl in dioxane (4 M; 4 mL, 16 mmol) was added and the mixture was heated at reflux for 1.5 h and then allowed to cool to room temperature. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 20-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and co-evaporated successively with methanol and diethyl ether. The residue was dried overnight under high vacuum at 70° C. to give (4S,7R)-2-(2,6-difluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (97 mg, 47%) as an off-white solid. ES(+)-MS (M+H) 319.

Provenance & Evidence