Hydrochloric Acid → HCID 57941465, compound

Participants

Reaction Conditions

Reaction Steps

Triethylamine (1 mL, 7.2 mmol) was added dropwise to a solution (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 1.00 g, 4.7 mmol) of in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of N′-(5-cyano-2-fluoro-phenyl)-N′-methyl-hydrazinecarboxylic acid tert-butyl ester (700 mg, 2.6 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 by preparative HPLC to give a yellow foam. This was triturated with ether and then petroleum ether and the solvent was removed. The residue was co-evaporated with methanol and the petroleum ether and then further purified on an ISCO system, eluting with 50-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, co-evaporated successively with methanol, diethyl ether, and petroleum ether, and then dried under high vacuum at room temperature to give 4-fluoro-3-((4S,7R)-1,7,8,8-tetramethyl-3-oxo-1,3,4,5,6,7-hexahydro-4,7-methano-indazol-2-yl)-benzonitrile (84 mg, 10%) as a white foam. APCI(+)-MS (M+H) 326.

Provenance & Evidence