Acetic Acid → 1H-Pyrazole-5-carboxylic acid, 1-methyl-3-propyl-, ethyl ester

HRID 1068684Notes

Reaction equation

HRID 1068684 reaction equation
C(O[C:4](=O)[C:5]([O:7][CH2:8][CH3:9])=[O:6])C.[CH3:11][C:12](=O)[CH2:13][CH2:14][CH3:15].[Na].C(O)(=O)C.[CH3:22][NH:23][NH2:24]>C(O)C>[CH3:22][N:23]1[C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:11][C:12]([CH2:13][CH2:14][CH3:15])=[N:24]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6061MethylhydrazineHCID 7268Diethyl OxalateHCID 78952-PentanoneHCID 5360545Sodium

Product 1

HCID 101765321H-Pyrazole-5-carboxylic acid, 1-methyl-3-propyl-, ethyl esterYield 15.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of diethyloxalate (27.2 ml, 0.2 mol) in 2-pentanone (21.2 ml, 0.2 mol) was added dropwise to a solution of sodium (4.83 g, 0.21 mol) in ethanol (200 ml), and the reaction stirred at 60° C. for 5 hours, then cooled in an ice-bath. The solution was neutralised using acetic acid (11.5 ml, 0.2 mol) and N-methyl hydrazine (10.6 ml, 0.2 mol) then added dropwise. The mixture was stirred for a further 4 hours at room temperature and concentrated under reduced pressure. The residue was partitioned between dichloromethane (300 ml) and water (200 ml), and the phases separated. The aqueous layer was extracted with dichloromethane (3×100 ml), the combined organic solutions were dried (MgSO4) and evaporated under reduced pressure. The crude is product was purified by column chromatography on silica gel, using ethyl acetate: hexane (25:75) as eluant to give ethyl 1-methyl-3-n-propyl-pyrazole-5-carboxylate (6.1 g) and the title compound (22.1 g, 56%). δ (CDCl3): 1.00 (3H, t), 1.40 (3H, t), 1.70 (2H, m), 2.60 (2H, t), 3.87 (3H, s), 4.40 (2H, q), 6.60 (1H, s).

Workup

  1. temperaturecooled in an ice-bath
  2. additionthen added dropwise
  3. stirringThe mixture was stirred for a further 4 hours at room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between dichloromethane (300 ml) and water (200 ml)
  6. customthe phases separated
  7. extractionThe aqueous layer was extracted with dichloromethane (3×100 ml)
  8. dry with materialthe combined organic solutions were dried (MgSO4)
  9. customevaporated under reduced pressure
  10. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-0a4c39ac23694dba93fb50157bebd93f
Source dataset
uspto-grants-2001_06
Patent number
US06251904B1

Reaction notes

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