Reaction #41161

Reaction equation

(Tetrahydro-pyran-4-yl)-hydrazine hydrochloride

ethyl (ethoxymethylene)-cyanoacetate

sodium acetate

→

5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carboxylic acid ethyl ester

Yield 92.3%

Solvents

ethanol

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Concentrationthe reaction was concentrated
3. 3
   Otherthe residue was partitioned between methylene chloride and water
4. 4
   OtherThe organic phase was separated
5. 5
   Washwashed with water
6. 6
   ExtractionEach aqueous phase was back extracted with methylene chloride
7. 7
   Dryingdried over sodium sulfate
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe crude material was purified by flash chromatography
10. 10
    Washeluting with 60-100% ethyl acetate/hexanes

Procedure

(Tetrahydro-pyran-4-yl)-hydrazine hydrochloride (1.975 g, 12.94 mmol), ethyl (ethoxymethylene)-cyanoacetate (1.958 g, 11.57 mmol) and sodium acetate (1.370 g; 16.70 mmol) were combined in ethanol (16 mL). The mixture was heated at 80-85° C. for 17 hours. After cooling to room temperature, the reaction was concentrated and the residue was partitioned between methylene chloride and water. The organic phase was separated and washed with water and then brine. Each aqueous phase was back extracted with methylene chloride. The two organic phases were combined, dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography eluting with 60-100% ethyl acetate/hexanes to give 5-amino-1-(tetrahydro-pyran-4-yl)-1H-pyrazole-4-carboxylic acid ethyl ester (2.554 g, 92%).

Source