反应详情

Triethylamine (26 mL, 186.5 mmol) was added dropwise 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; 13.33 g, 62.1 mmol) in dichloromethane (150 mL), yielding a thick suspension. This was stirred for 3 min and then N′-(2,5-dichloro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 34; 13.00 g, 46.9 mmol) was added in one portion. The cooling bath was removed and the reaction mixture was stirred at room temperature for 10 min, then in an oil-bath at 50° C. for 4 h. The reaction mixture was cooled to room temperature, then added to water (200 mL) and extracted with dichloromethane (3×150 mL). The combined organic layers were washed with brine (200 mL), dried (magnesium sulfate), filtered, and evaporated to give N′-(2,5-dichloro-phenyl)-N′-((1R,4R)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (29.55 g, 138% of the expected amount) as a brown oil. This was used directly in the next step without further purification.

1. customyielding a thick suspension
2. customThe cooling bath was removed
3. stirringthe reaction mixture was stirred at room temperature for 10 min
4. waitin an oil-bath at 50° C. for 4 h
5. additionadded to water (200 mL)
6. extractionextracted with dichloromethane (3×150 mL)
7. washThe combined organic layers were washed with brine (200 mL)
8. dry with materialdried (magnesium sulfate)
9. filtrationfiltered
10. customevaporated