反应详情

Triethylamine (21.3 mL, 153 mmol) was added in two portions 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; 10.9 g, 51 mmol) in dichloromethane (100 mL), giving a thick suspension. Dichloromethane (30 mL) was added, followed by N′-(2-chloro-4-fluoro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 33; 9.8 g, 37.6 mmol). The reaction mixture was placed in an oil-bath at 50° C., heated at this temperature for 6 hours and then allowed to cool to room temperature and stir for 1 h. The reaction mixture was poured into water (200 mL) and two layers were separated. The organic layer was washed with water (2×200 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated, and then dried under high vacuum for 90 min to give N′-(2-chloro-4-fluoro-phenyl)-N′-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (14.9 g, 90%) as a pale foam.

1. customgiving a thick suspension
2. customThe reaction mixture was placed in an oil-bath at 50° C.
3. temperatureheated at this temperature for 6 hours
4. customwere separated
5. washThe organic layer was washed with water (2×200 mL) and brine (100 mL)
6. dry with materialdried (magnesium sulfate)
7. filtrationfiltered
8. customevaporated
9. customdried under high vacuum for 90 min