反应详情

温度

0 °C

Triethylamine (3.9 mL; 28 mmol) was added over a period of 2-3 min to a cooled (0° C.) solution of (1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride (Intermediate 25; 2.2 g, 10.2 mmol) in dichloromethane (25 mL), resulting in a heavy precipitate. Dichloromethane (10 mL) was added, followed by N′-(2-chloro-4-fluoro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 33; 1.87 g, 7.2 mmol). The reaction mixture was stirred at 0° C. for 5 min, and then at 50° C. (oil-bath temperature) over the weekend. Dichloromethane was added and the solution was washed with water (3×50 mL) and brine (50 mL), dried (magnesium sulfate, filtered, evaporated, and dried under high vacuum to give N′-(2-chloro-4-fluoro-phenyl)-N′-((1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (3.8 g, 120% of the expected amount). This was used directly in the next step without further purification.

1. customresulting in a heavy precipitate
2. customat 50° C.
3. washthe solution was washed with water (3×50 mL) and brine (50 mL)
4. dry with materialdried (magnesium sulfate
5. filtrationfiltered
6. customevaporated
7. customdried under high vacuum