Hydrochloric Acid → HCID 57941406, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.82 mL, 5.9 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; 690 mg, 3.21 mmol) in 1,2-dichloroethane (6 mL) over 1 min. A solution of N′-(2-cyano-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (435 mg, 1.76 mmol) in 1,2-dichloroethane (10 mL) was added. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 15 min, and then in an oil bath at 50° C. for 1 h. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 6 mL, 24 mmol) was added and the mixture was heated in an oil bath at 50° C. for 30 min and then at 100° C. for 1 h and allowed to cool. Dichloromethane (150 mL) was added and the mixture was washed with 1:1 water/brine (30 mL), dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 50-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with methanol and then diethyl ether. The residue was dried under high vacuum at 70° C. to give 2-((4S,7R)-1,7,8,8-tetramethyl-3-oxo-1,3,4,5,6,7-hexahydro-4,7-methano-indazol-2-yl)-benzonitrile (55 mg, 10%) as an off-white solid. ES(+)-MS (M+H) 308.

Provenance & Evidence