反应详情

温度

50 °C

Triethylamine (840 μL, 6.0 mmol) was added 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; 612 mg, 2.9 mmol) in 1,2-dichloroethane (8 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of N′-(2,4-bis-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (646 mg, 1.8 mmol) in 1,2-dichloroethane (14 mL) was added. The reaction mixture was stirred at 0° C. for 15 min, at room temperature for 30 min, and then in an oil bath at 50° C. for 30 min. An additional portion of (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 20; 0.6 g, 2.8 mmol) in 1,2-dichloroethane (6 mL) was added and the mixture was heated at 50° C. for 45 min. The reaction mixture was allowed to cool. A solution of HCl in dioxane (4 M; 8 mL, 32 mmol) was added and the reaction mixture was heated at reflux for 1 h, allowed to cool, poured into water (200 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (magnesium sulfate), filtered, evaporated, and chromatographed, eluting with 40% ethyl acetate/hexanes) to give (4S,7R)-2-(2,4-bis-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (501 mg, 66%) as an off-white solid. APCI(+)-MS (M+H) 419.

1. stirringThe reaction mixture was stirred at 0° C. for 15 min, at room temperature for 30 min
2. waitin an oil bath at 50° C. for 30 min
3. temperatureto cool
4. temperaturethe reaction mixture was heated
5. temperatureat reflux for 1 h
6. temperatureto cool
7. extractionextracted with ethyl acetate (3×50 mL)
8. dry with materialThe combined organic layers were dried (magnesium sulfate)
9. filtrationfiltered
10. customevaporated
11. customchromatographed
12. washeluting with 40% ethyl acetate/hexanes)