反应详情

温度

100 °C

Triethylamine (518 μL, 3.7 mmol) was added dropwise to a cooled (0° C.) solution (1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (418 mg, 1.95 mmol) of in 1,2-dichloroethane (3 mL) over 1 min. The reaction mixture was stirred for 5 min and then a solution of N′-(2-fluoro-5-trifluoromethyl-phenyl)-N-methyl-hydrazinecarboxylic acid tert-butyl ester (380 mg, 1.23 mmol) in 1,2-dichloroethane (6 mL) was added over 2 min. 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 2 h. A solution of HCl in dioxane (4 M; 8 mL, 32 mmol) was added and the mixture was heated in an oil bath at 100° C. for 1 h and then allowed to cool to room temperature. Dichloromethane (100 mL) was added and the mixture was washed with 1:1 water/brine (20 mL), dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 20-50% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, and then co-evaporated with ether and then petroleum ether. The residue was triturated with hexanes, and the solid was dried under high vacuum at 70° C. overnight and then at 85° C. for 1 h to give (4S,7R)-2-(2-fluoro-5-trifluoromethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (142 mg, 30%) as a light yellow solid. ES(+)-MS (M+H) 369.

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 2 h
3. temperatureto cool to room temperature
4. washthe mixture was washed with 1:1 water/brine (20 mL)
5. dry with materialdried (magnesium sulfate)
6. filtrationfiltered
7. customevaporated
8. custompurified
9. washeluting with 20-50% ethyl acetate/hexanes
10. customFractions homogeneous for the product were evaporated
11. customThe residue was triturated with hexanes
12. customthe solid was dried under high vacuum at 70° C. overnight