Reaction #41164

Reaction equation

Cyclopentyl-hydrazine hydrochloride

ethyl (ethoxymethylene)-cyanoacetate

sodium acetate

→

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

Yield 79.3%

Solvents

ethanol

Conditions

Workup

1. 1
   TemperatureAfter cooling to room temperature
2. 2
   Otherethanol was removed in vacuo
3. 3
   Otherthe residue was partitioned between methylene chloride and water
4. 4
   WashThe organic phase was washed sequentially with water and brine
5. 5
   ExtractionEach aqueous phase was back extracted with a single portion of methylene chloride
6. 6
   Dryingdried over sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   OtherPurification by flash chromatography
9. 9
   Washeluting with 10-40% EtOAc/hexanes

Procedure

Cyclopentyl-hydrazine hydrochloride (1.000 g; 7.32 mmol), ethyl (ethoxymethylene)-cyanoacetate (1.026 g, 6.61 mmol) and anhydrous sodium acetate (0.644 g, 7.85 mmol) were combined in ethanol (10 mL) and heated at 70° C. for 20 hours. After cooling to room temperature, ethanol was removed in vacuo and the residue was partitioned between methylene chloride and water. The organic phase was washed sequentially with water and brine. Each aqueous phase was back extracted with a single portion of methylene chloride. The two organic phases were combined, dried over sodium sulfate and concentrated. Purification by flash chromatography, eluting with 10-40% EtOAc/hexanes yielded 5-amino-1-cyclopentyl-1H-pyrazole-4-carboxylic acid ethyl ester (1.170 g, 73%). Mass spectrum: m/z: 224.1 (M+H).

Source