Reaktion #41154

Reaktionsgleichung

2-(5-chloro-isoxazole-3-carbonyl)-3-dimethylamino-acrylic acid ethyl ester

tert-butylhydrazine hydrochloride

sodium acetate

→

1-tert-butyl-5-(5-chloro-isoxazol-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAt this time, the reaction was cooled to 25° C.
2. 2
   Einengenwas concentrated in vacuo
3. 3
   SonstigeThe reaction was partitioned between water (200 mL) and dichloromethane (2×50 mL)
4. 4
   WaschenThe combined organics were washed with a saturated aqueous sodium chloride solution
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo

Vorschrift

A solution of 2-(5-chloro-isoxazole-3-carbonyl)-3-dimethylamino-acrylic acid ethyl ester (294.8 mg, 1.08 mmol) in absolute ethanol (1.4 mL, 0.77M) was treated with tert-butylhydrazine hydrochloride (137.3 mg, 1.10 mmol) and sodium acetate (108.6 mg, 1.32 mmol). The resulting mixture was heated to 90° C. overnight. At this time, the reaction was cooled to 25° C. and was concentrated in vacuo. The reaction was partitioned between water (200 mL) and dichloromethane (2×50 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Biotage chromatography (40S column 60% ethyl acetate/hexanes) followed by ISCO CombiFlash (4 g column 0-20% ethyl acetate/hexanes) afforded 1-tert-butyl-5-(5-chloro-isoxazol-3-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (67.4 g, 21%) as a yellow oil.

Quelle