反应详情

温度

100 °C

A mixture of (4S,7R)-7,8,8-trimethyl-2-(2-trifluoromethyl-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 22; 710 mg, 2.1 mmol) and iodomethane (0.33 mL, 5.3 mmol) in N,N-dimethylformamide (5 mL) in a sealed tube was heated at 100° C. overnight. Water was added and the reaction mixture was extracted three times with ethyl acetate. The combined organic extracts were washed with water and brine, dried (magnesium sulfate), filtered, evaporated, and purified using an Analogix Intelliflash 280 system (Analogix, Inc., Burlington, Wis.) with an Analytical Sales Aspire 90 g column, eluting with 25-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, dissolved in ethyl acetate and heated at reflux with activated charcoal for 10 min. The mixture was filtered through Celite® and evaporated to give (4S,7R)-1,7,8,8-tetramethyl-2-(2-trifluoromethyl-phenyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (602 mg, 81%) as a light yellow solid. ES(+)-MS (M+H) 351.

1. extractionthe reaction mixture was extracted three times with ethyl acetate
2. washThe combined organic extracts were washed with water and brine
3. dry with materialdried (magnesium sulfate)
4. filtrationfiltered
5. customevaporated
6. custompurified
7. washeluting with 25-100% ethyl acetate/hexanes
8. customFractions homogeneous for the product were evaporated
9. dissolutiondissolved in ethyl acetate
10. temperatureheated
11. temperatureat reflux with activated charcoal for 10 min
12. filtrationThe mixture was filtered through Celite®
13. customevaporated