反应详情

温度

50 °C

N′-(2-Trifluoromethyl-phenyl)-hydrazinecarboxylic acid tert-butyl ester (1.85 g, 6.6 mmol) was added in one portion to a ice-bath-cooled solution of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 1.09 g, 5.1 mmol) in a mixture of 1,2-dichloroethane (12 mL) and pyridine (0.6 mL, 7.6 mmol). The mixture was diluted with 1,2-dichloroethane (6 mL) to facilitate stirring. The reaction mixture was heated at 50° C. for 1 h, then cooled to room temperature. A 4 M solution of HCl in dioxane (3.6 mL) was added via the condenser and the solution was stirred for several minutes. Glacial acetic acid (7 mL) was added and the reaction mixture was heated in an oil bath at ˜100° C. for 2 h. The reaction mixture was stirred overnight at room temperature and then evaporated. Dichloromethane was added and the solution was washed twice with brine. The aqueous washes were back-extracted with dichloromethane, and the combined organic layers were washed with brine, dried (magnesium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an Analytical Sales Aspire 120 g column, eluting with 0-40% ethyl acetate/hexanes to give (4S,7R)-2-(2-trifluoromethyl-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (0.80 g, 46%) as a light brown solid.

1. temperaturecooled to room temperature
2. stirringthe solution was stirred for several minutes
3. temperaturethe reaction mixture was heated in an oil bath at ˜100° C. for 2 h
4. stirringThe reaction mixture was stirred overnight at room temperature
5. customevaporated
6. additionDichloromethane was added
7. washthe solution was washed twice with brine
8. extractionThe aqueous washes were back-extracted with dichloromethane
9. washthe combined organic layers were washed with brine
10. dry with materialdried (magnesium sulfate)
11. filtrationfiltered
12. customevaporated
13. custompurified
14. washeluting with 0-40% ethyl acetate/hexanes