Hydrochloric Acid → HCID 57941488, 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; 415 mg, 1.93 mmol) in 1,2-dichloroethane (12 mL) was added to a cooled (0° C.) solution of triethylamine (380 μL, 2.73 mmol) and N′-(2,5-bis-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (480 mg, 1.34 mmol) in 1,2-dichloroethane (8 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 45 min. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the mixture was heated at reflux for 1.5 h and then allowed to cool to room temperature. Dichloromethane (75 mL) and 1:1 water/brine (20 mL) were added. The mixture was shaken and the layers separated. The aqueous layer was back-extracted with dichloromethane (30 mL). The combined organic layers were dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO40 g column, eluting with 40-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, co-evaporated successively with methanol and ether, and then dried under high vacuum at 95° C. to give (4S,7R)-2-(2,5-bis-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (256 mg, 46%) as an off-white solid. ES(+)-MS (M+H) 419.

Provenance & Evidence