Hydrochloric Acid → HCID 16116995, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (1 mL, 7.2 mmol) was added dropwise to a solution of N′-(3-chloro-2-fluoro-phenyl)-N′-methyl-hydrazinecarboxylic acid tert-butyl ester (434 mg, 1.6 mmol) in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 800 mg, 3.7 mmol) in 1,2-dichloroethane (14 mL) was added over 2 min. The reaction mixture was heated 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; 6 mL, 24 mmol) was added and the mixture was heated at reflux for 1.5 h and then allowed to cool to room temperature. The solvent was evaporated and the residue was purified on an ISCO system, eluting with 30-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and co-evaporated with methanol. The residue was triturated with ether/hexane and the solvent was removed with a pipet. The solid was drie under high vacuum at 90° C. to give (4S,7R)-2-(3-chloro-2-fluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (37 mg, 7%) as a white solid. ES(+)-MS (M+H) 335.

Provenance & Evidence