反应详情

温度

0 °C

Triethylamine (120 μL, 0.86 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; 90 mg, 0.42 mmol) in 1,2-dichloroethane (1 mL) over 1 min. A solution of N-cyclopropyl-N′-phenyl-hydrazinecarboxylic acid tert-butyl ester (66 mg, 0.27 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 90 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. A further portion of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the mixture was heated in an oil bath at 100° C. for 2 h. The solvent was evaporated. Dichloromethane (30 mL) was added and the mixture was washed with 1:1 water/brine (10 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 25-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with dichloromethane and then petroleum ether. The residue was dried under high vacuum at 75° C. overnight to give (4S,7R)-1-cyclopropyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (35 mg, 43%) as a light yellow solid. APCI(+)-MS (M+H) 309.

1. waitin an oil bath at 50° C. for 90 min
2. temperatureThe reaction mixture was cooled
3. temperaturethe mixture was heated in an oil bath at 100° C. for 1 h
4. temperaturethe mixture was heated in an oil bath at 100° C. for 2 h
5. customThe solvent was evaporated
6. additionDichloromethane (30 mL) was added
7. washthe mixture was washed with 1:1 water/brine (10 mL)
8. dry with materialdried (magnesium sulfate)
9. filtrationfiltered
10. customevaporated
11. custompurified
12. washeluting with 25-100% ethyl acetate/hexanes
13. customFractions homogeneous for the product were evaporated
14. customThe residue was dried under high vacuum at 75° C. overnight