Reaktion #41198

Reaktionsgleichung

tert-butyl nitrite

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

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

HCl

→

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

Lösungsmittel

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   workup.WAITat 60° C. for 2 h
3. 3
   TemperaturThe mixture was cooled to room temperature
4. 4
   Extraktionextracted with dichloromethane
5. 5
   ExtraktionThe aqueous layer was extracted three times with dichloromethane
6. 6
   EinengenAfter the combined organic layers were concentrated in vacuo
7. 7
   Sonstigethe crude residue was purified by flash chromatography
8. 8
   Wascheneluting with a gradient of 10-20% ethyl acetate/hexanes
9. 9
   EinengenThe desired fractions were concentrated in vacuo
10. 10
    Sonstigedried under vacuum

Vorschrift

To a mixture of tert-butyl nitrite (5.1 mL, 38.7 mmol), cuprous chloride (3.8 g, 38.7 mmol), and anhydrous acetonitrile (100 mL) was added a mixture of 5-amino-1-cyclobutyl-1H-pyrazole-4-carboxylic acid ethyl ester and 3-amino-1-cyclobutyl-1H-pyrazole-4-carboxylic acid ethyl ester (from last step without further purification) in anhydrous acetonitrile (50 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 then poured into 6N HCl (50 mL) and extracted with dichloromethane. The aqueous layer was extracted three times with dichloromethane. After the combined organic layers 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. The desired fractions were concentrated in vacuo and dried under vacuum to give 5-chloro-1-cyclobutyl-1H-pyrazole-4-carboxylic acid ethyl ester (eluted first, 610 mg, 10.3%) and 3-chloro-1-cyclobutyl-1H-pyrazole-4-carboxylic acid ethyl ester (eluted later, 147 mg, 2.5%). LRMS m/z calcd for C10H13ClN2O2 (M+H) 229.1, found 229.1.

Quelle