反应详情

温度

0 °C

Triethylamine (43 mL, 309 mmol) was added over 2-3 min 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; 23.2 g, 103.8 mmol) in dry dichloromethane (260 mL), yielding a heavy precipitate. Dichloromethane (25 mL) was added, followed by N′-(2-chloro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 30; 19.36 g, 79.8 mmol) in one portion. Dichloromethane (35 mL) was added and the mixture was stirred at 0° C. for 5 min and then heated in an oil bath at 50° C. for 4 h. The mixture was poured into cold water (500 mL) and the layers were separated. The aqueous layer was extracted with dichloromethane (2×300 mL) and the combined organic layers were washed with brine (200 mL), dried (magnesium sulfate), filtered, evaporated, and purified by silica gel chromatography, eluting with 20-100% ethyl acetate/petroleum ether. Fractions homogeneous for the product were evaporated and dried under high vacuum to give N′-(2-chloro-phenyl)-N′-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (23.4 g, 70%) as a pale foam.

1. customyielding a heavy precipitate
2. temperatureheated in an oil bath at 50° C. for 4 h
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with dichloromethane (2×300 mL)
5. washthe combined organic layers were washed with brine (200 mL)
6. dry with materialdried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. custompurified by silica gel chromatography
10. washeluting with 20-100% ethyl acetate/petroleum ether
11. customFractions homogeneous for the product were evaporated
12. customdried under high vacuum