Reaktion #41173

Reaktionsgleichung

sodium acetate

4-Hydrazino-cyclohexanol, hydrochloride

4-hydrazino-cyclohexanol hydrochloride

2-dimethylaminomethylene-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester

→

cis-1-(4-hydroxy-cyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester

Ausbeute 27.0%

trans-1-(4-hydroxy-cyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester

Ausbeute 18.0%

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to room temperature
2. 2
   Sonstigethe reaction mixture was partitioned between methylene chloride and water
3. 3
   WaschenThe aqueous phase was washed a second time with methylene chloride
4. 4
   Waschenwashed with brine
5. 5
   Trocknendried over sodium sulfate
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigePurification by flash chromatography (
8. 8
   Wascheneluting with a 40-100% ethyl acetate-hexanes gradient)
9. 9
   Sonstigesuccessfully separated the cis-trans isomers

Vorschrift

4-Hydrazino-cyclohexanol, hydrochloride (0.255 g, 1.53 mmol, prepared in Example 67, Step 2), 2-dimethylaminomethylene-4,4,4-trifluoro-3-oxo-butyric acid ethyl ester (0.272 g, 1.14 mmol) and anhydrous sodium acetate (0.256 g, 3.12 mmol) were combined in ethanol (2.0 mL) and heated at 70° C. under argon for 14 hours. After cooling to room temperature, the reaction mixture was partitioned between methylene chloride and water. The aqueous phase was washed a second time with methylene chloride. The two organic phases were combined, washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification by flash chromatography (eluting with a 40-100% ethyl acetate-hexanes gradient) successfully separated the cis-trans isomers, yielding cis-1-(4-hydroxy-cyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (96.1 mg, 27%) and trans-1-(4-hydroxy-cyclohexyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid ethyl ester (63.5 mg, 18%).

Quelle