反应详情

温度

0 °C

Oxalyl chloride (34 mL, 390 mmol) and N,N-dimethylformamide (4-5 drops) were added sequentially to a solution of (1S,4S)-3-camphorcarboxylic acid (Intermediate 24; 25.75 g, 131 mmol) in dichloromethane (130 mL) at 0° C. The reaction mixture was stirred at 0° C. for 20 min and then at room temperature for 2.5 h. The solvent was evaporated, and the residue was co-evaporated four times with dichloromethane and then dried under high vacuum to give crude (1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl chloride. The crude acid chloride was dissolved in dichloromethane (340 mL) at 0° C., and triethylamine (42 mL, 301 mmol) was added. The mixture was stirred at 0° C. for 5 min, and then N′-(2,4-difluoro-phenyl)-hydrazinecarboxylic acid tert-butyl ester (Intermediate 32; 24.5 g, 100.4 mmol) was added. The mixture was stirred at 0° C. for 5 min, at reflux for 2.5 h, and then at room temperature for 2 days. Dichloromethane (250 mL) and water (250 mL) were added and the layers were separated. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic layers were dried (magnesium sulfate), filtered and evaporated to give crude N′-(2,4-difluoro-phenyl)-N′-((1S,4S)-4,7,7-trimethyl-3-oxo-bicyclo[2.2.1]heptane-2-carbonyl)-hydrazinecarboxylic acid tert-butyl ester (66.5 g, 157% of the expected amount) as a black oil which was used directly in the next step.

1. waitat room temperature for 2.5 h
2. customThe solvent was evaporated
3. customdried under high vacuum