反应详情

A solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 460 mg, 2.14 mmol) in 1,2-dichloroethane (12 mL) was added to a cooled (0° C.) solution of triethylamine (410 μL, 2.94 mmol) and N-methyl-N′-naphthalen-2-yl-hydrazinecarboxylic acid tert-butyl ester (Intermediate 36; 430 mg, 1.58 mmol) in 1,2-dichloroethane (6 mL) over 1 min. The reaction mixture was stirred at room temperature for 30 min. A solution of HCl in dioxane (4 M; 10 mL, 40 mmol) was added and the reaction mixture was heated in an oil-bath at 100° C. for 30 min, and allowed to cool. The solvent was evaporated and dichloromethane (100 mL) was added. The solution was washed with 1:1 water/brine (30 mL) and the aqueous wash was back-extracted with dichloromethane (30 mL). The combined organic layers were dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting 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 40° C. to give (4S,7R)-1,7,8,8-tetramethyl-2-naphthalen-2-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (337 mg, 64%) as an off-white foam. ES(+)-MS (M+H) 333.

1. temperaturethe reaction mixture was heated in an oil-bath at 100° C. for 30 min
2. temperatureto cool
3. customThe solvent was evaporated
4. additiondichloromethane (100 mL) was added
5. washThe solution was washed with 1:1 water/brine (30 mL)
6. washthe aqueous wash
7. extractionwas back-extracted with dichloromethane (30 mL)
8. dry with materialThe combined organic layers were dried (magnesium sulfate)
9. filtrationfiltered
10. customevaporated
11. custompurified
12. washeluting with 60-100% ethyl acetate/hexanes
13. customFractions homogeneous for the product were evaporated
14. dry with materialwith diethyl ether, and dried under high vacuum at 40° C.