反应详情

Triethylamine (3 mL, 21.5 mmol) was added dropwise 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; 1.50 g, 7.0 mmol) in dichloromethane (18 mL), yielding a thick suspension. This was stirred for 3 min and then N′-(2-fluoro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 29; 1.20 g, 5.3 mmol) was added in one portion. The reaction mixture was allowed to warm to room temperature and stir for 2.5 h. The mixture was added to water (50 mL) and extracted with dichloromethane (3×40 mL). The combined organic layers were washed with brine (30 mL), dried (magnesium sulfate), filtered, evaporated, and dried under high vacuum at room temperature for 30 min to give N′-(2-fluoro-phenyl)-N′-((1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (2.67 g, 124% of the expected amount) as an orange foam. This was used directly in the next step without further purification.

1. customyielding a thick suspension
2. stirringstir for 2.5 h
3. extractionextracted with dichloromethane (3×40 mL)
4. washThe combined organic layers were washed with brine (30 mL)
5. dry with materialdried (magnesium sulfate)
6. filtrationfiltered
7. customevaporated
8. customdried under high vacuum at room temperature for 30 min