反应详情

Triethylamine (4.8 mL, 34.2 mmol) and tert-butyl hydrazine hydrochloride (1.4 g, 11.4 mmol) were added sequentially to a solution of crude 2-cyclopropanecarbonyl-3-dimethylamino-acrylic acid methyl ester (2.4 g, 11.4 mmol) in ethanol (24 mL). The resulting suspension was mixed well and divided equally into two 25 mL Personal Chemistry Microwave Process Tubes (Biotage AB, Sweden). The tubes were sealed with a septum and submitted to 150 W microwave irradiation using a Personal Chemistry Microwave Synthesis System (Biotage AB, Sweden) at 160° C. for 30 minutes. The reaction mixtures in the two tubes were combined and ethanol was evaporated under reduced pressure. The remaining mixture was partitioned between dichloromethane and water, and the water phase was extracted three times with dichloromethane. The organic phases were combined, concentrated in vacuo, and purified by silica chromatography eluting with a gradient of 10-20% ethyl acetate/hexanes, then 20% ethyl acetate/hexanes to give 1-tert-butyl-5-cyclopropyl-1H-pyrazole-4-carboxylic acid methyl ester (921 mg, 36%). LRMS m/z calcd for C12H18N2O2 (M+H) 223.1, found 223.1.

1. additionThe resulting suspension was mixed well
2. customThe tubes were sealed with a septum
3. customsubmitted to 150 W microwave irradiation
4. customa Personal Chemistry Microwave Synthesis System (Biotage AB, Sweden) at 160° C. for 30 minutes
5. customethanol was evaporated under reduced pressure
6. customThe remaining mixture was partitioned between dichloromethane and water
7. extractionthe water phase was extracted three times with dichloromethane
8. concentrationconcentrated in vacuo
9. custompurified by silica chromatography
10. washeluting with a gradient of 10-20% ethyl acetate/hexanes