反应详情

To a mixture of t-butyl nitrite (2.03 mL, 15.38 mmol), cuprous chloride (1.52 g, 15.38 mmol), and anhydrous acetonitrile (30 mL) was added the solution of the mixture of 5-amino-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester and 3-amino-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester (from last step) in anhydrous acetonitrile (20 mL) at 0° C. The reaction mixture was stirred at room temperature for 1 h and then at 60° C. for 2 h. The mixture was cooled to room temperature and poured into 6N HCl (20 mL) and extracted with dichloromethane. The aqueous phase was extracted three times with dichloromethane. After the combined organic phases were concentrated in vacuo, the crude residue was purified by flash chromatography eluting with a gradient of 10-20% ethyl acetate/hexanes, then 20% ethyl acetate/hexanes to give 5-chloro-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester (eluted first, 296 mg, 13%) and 3-chloro-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester (eluted later, 159 mg, 7%). LRMS m/z calcd for C9H11ClN2O2 (M+H) 215.1, found 215.1.

1. additionwas added
2. waitat 60° C. for 2 h
3. temperatureThe mixture was cooled to room temperature
4. extractionextracted with dichloromethane
5. extractionThe aqueous phase was extracted three times with dichloromethane
6. concentrationAfter the combined organic phases were concentrated in vacuo
7. customthe crude residue was purified by flash chromatography
8. washeluting with a gradient of 10-20% ethyl acetate/hexanes