反应详情

A solution of (1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 25; 530 mg, 2.47 mmol) in 1,2-dichloroethane (12 mL) was added to a cooled (0° C.) solution of triethylamine (470 μL, 3.37 mmol) and N-methyl-N′-naphthalen-2-yl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 36; 450 mg, 1.65 mmol) in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred at room temperature for 90 min. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the reaction mixture was heated at reflux for 90 min, and allowed to cool. The solvent was evaporated. The residue was purified twice using ISCO 40 g columns. The first column was eluted with 50-100% ethyl acetate and then with 10% methanol/ethyl acetate. The second column was eluted with 60-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated and the residue was co-evaporated with methanol and then with diethyl ether, and dried under high vacuum at room temperature to give (4R,7S)-1,7,8,8-tetramethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (170 mg, 31%) as an off-white foam. ES(+)-MS (M+H) 333.

1. temperaturethe reaction mixture was heated
2. temperatureat reflux for 90 min
3. temperatureto cool
4. customThe solvent was evaporated
5. customThe residue was purified twice using ISCO 40 g columns
6. washThe first column was eluted with 50-100% ethyl acetate
7. washThe second column was eluted with 60-100% ethyl acetate/hexanes
8. customFractions homogeneous for the product were evaporated
9. dry with materialwith diethyl ether, and dried under high vacuum at room temperature