Acetic Acid → ethyl 1-isopropyl-1H-pyrazole-3-carboxylate

HRID 532832Notes

Reaction equation

HRID 532832 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[CH:9][NH:8][N:7]=1)=[O:5])[CH3:2].I[CH:12]([CH3:14])[CH3:13].CC[O-].[Na+].CC(O)=O>C1COCC1.O>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[CH:9][N:8]([CH:12]([CH3:14])[CH3:13])[N:7]=1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6362Isopropyl iodideHCID 2723922Sodium ethoxideHCID 178469268HCID 178469268, compound

Product 1

HCID 23005998ethyl 1-isopropyl-1H-pyrazole-3-carboxylateYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To 1H-pyrazole-3-carboxylic acid ethyl ester (23.1 g, 165 mmol) in THF (330 mL) was added 2-iodopropane (33.0 mL, 330 mmol) followed by NaOEt (21% in EtOH, 65.0 mL, 174 mmol). This solution was then heated to reflux for 16 h. The reaction was then allowed to cool to room temperature. AcOH (10.5 mL, 183 mmol) was added and the reaction was stirred for 5 min. H2O (400 mL) was added to the solution, and this mixture was extracted with EtOAc (3×150 mL). The combined organic was washed with sat. aq. NaHCO3, then brine. The organic was dried over MgSO4, filtered, and concentrated to give the product (28.70 g, 96%) as a brown oil containing a 98:2 mixture of regioisomers by 1H NMR.

Workup

  1. temperatureThis solution was then heated
  2. temperatureto reflux for 16 h
  3. extractionthis mixture was extracted with EtOAc (3×150 mL)
  4. washThe combined organic was washed with sat. aq. NaHCO3
  5. dry with materialThe organic was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-745281b5643741f2b75cd2e3cf769d82
Source dataset
uspto-grants-2014_10
Patent number
US08853202B2

Reaction notes

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