Hydrochloric Acid → (4S,7R)-1,7,8,8-tetramethyl-2-(4-methyl-naphthalen-1-yl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

Participants

Reaction Conditions

Reaction Steps

Triethylamine (0.18 mL, 1.29 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; 160 mg, 0.75 mmol) in 1,2-dichloroethane (2 mL) over 1 min. A solution of N-methyl-N′-(4-methyl-naphthalen-1-yl)-hydrazinecarboxylic acid tert-butyl ester (74 mg, 0.26 mmol) in 1,2-dichloroethane (4 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 30 min. The reaction mixture was cooled. A solution of HCl in dioxane (4 M; 4 mL, 16 mmol) was added and the mixture was heated in an oil bath at 100° C. for 1 h and allowed to cool. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 40-100% 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. overnight to give (4S,7R)-1,7,8,8-tetramethyl-2-(4-methyl-naphthalen-1-yl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (33 mg, 37%) as a light brown solid. ES(+)-MS (M+H) 347.

Provenance & Evidence