反应详情

温度

100 °C

A mixture of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 355 mg, 1.16 mmol) and ethyl iodoacetate (700 μL, 5.91 mmol) in dimethylformamide (5 mL) was heated at 100° C. for 2 h. The solvent was evaporated, dichloromethane (50 mL) was added and the solution was washed with 1:1 water/aqueous sodium thiosulfate (25 mL). The aqueous layer was back-extracted with dichloromethane (2×25 mL) and the combined organic layers were washed with brine (25 mL). The solution was dried (magnesium sulfate), filtered, evaporated, purified using an ISCO 12 g column, eluting with 40-100% ethyl acetate/petroleum ether, and dried under high vacuum at 75° C. to give [(4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-3-oxo-2,3,4,5,6,7-hexahydro-4,7-methano-indazol-1-yl]-acetic acid ethyl ester (269 mg, 59%) as an off-white solid. ES(+)-MS (M+H) 391.

1. customThe solvent was evaporated
2. additiondichloromethane (50 mL) was added
3. washthe solution was washed with 1:1 water/aqueous sodium thiosulfate (25 mL)
4. extractionThe aqueous layer was back-extracted with dichloromethane (2×25 mL)
5. washthe combined organic layers were washed with brine (25 mL)
6. dry with materialThe solution was dried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. custompurified
10. washeluting with 40-100% ethyl acetate/petroleum ether
11. customdried under high vacuum at 75° C.