تفاعل #41188

معادلة التفاعل

HCl

5-amino-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester

3-amino-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester

t-butyl nitrite

→

5-chloro-1-cyclopropyl-1H-pyrazole-4-carboxylic acid ethyl ester

المذيبات

acetonitrile

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added
2. 2
   workup.WAITat 60° C. for 2 h
3. 3
   درجة الحرارةThe mixture was cooled to room temperature
4. 4
   استخلاصextracted with dichloromethane
5. 5
   استخلاصThe aqueous phase was extracted three times with dichloromethane
6. 6
   تركيزAfter the combined organic phases were concentrated in vacuo
7. 7
   أخرىthe crude residue was purified by flash chromatography
8. 8
   غسيلeluting with a gradient of 10-20% ethyl acetate/hexanes

الإجراء التجريبي

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.

المصدر