Ethyl Acetoacetate → 2-(4-Methoxyphenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one

HRID 847419Notes

Reaction equation

HRID 847419 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][NH2:11])=[CH:6][CH:5]=1.O.O.O.C([O-])(=O)C.[Na+].[C:20](OCC)(=[O:25])[CH2:21][C:22]([CH3:24])=O>C(O)C>[CH3:24][C:22]1[CH2:21][C:20](=[O:25])[N:10]([C:7]2[CH:8]=[CH:9][C:4]([O:3][CH3:2])=[CH:5][CH:6]=2)[N:11]=1

Participants

5

Reactant 3

HCID 8868Ethyl AcetoacetateHCID 27239044-Methoxyphenylhydrazine hydrochlorideHCID 23665404Sodium Acetate Trihydrate

Product 1

HCID 1247322-(4-Methoxyphenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-oneYield 42.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4-Methoxy-phenylhydrazine hydrochloride (5.6 g, 32 mmol; product of Aldrich Chem. Co.), sodium acetate trihydrate (5.45 g, 40 mmol; product of Kishida Chemicals) and ethyl acetoacetate (4.16 g, 32 mmol; product of Kishida Chemicals) were dissolved in 40 ml ethanol, and the solution was heated under reflux for two hours to complete the reaction. After cooling, the solvent was distilled off from the reaction mixture under reduced pressure, 40 ml ethanol was added to the residue, and the insoluble matters were removed by filtration. The filtrate was concentrated to dryness under reduced pressure, the residue was dissolved in a small volume of a solvent mixture of benzene and ethyl acetate (4:1), and the solution was subjected to silica gel chromatography (150 g of Silica Gel 60; product of Merck) Elution was performed by using a solvent mixture of benzene and ethyl acetate (4:1), the eluate was concentrated to dryness under reduced pressure, and the residue was recrystallized with methanol, giving 2.80 g (yield: 42.9%) of PMPMP. Its structure was confirmed by 1H NMR and 13C NMR. The spectra thus obtained are shown in Table 1 below.

Workup

  1. temperaturethe solution was heated
  2. temperatureunder reflux for two hours
  3. customthe reaction
  4. temperatureAfter cooling
  5. distillationthe solvent was distilled off from the reaction mixture under reduced pressure, 40 ml ethanol
  6. additionwas added to the residue
  7. customthe insoluble matters were removed by filtration
  8. concentrationThe filtrate was concentrated to dryness under reduced pressure
  9. dissolutionthe residue was dissolved in a small volume of a solvent mixture of benzene and ethyl acetate (4:1)
  10. washthe solution was subjected to silica gel chromatography (150 g of Silica Gel 60; product of Merck) Elution
  11. additiona solvent mixture of benzene and ethyl acetate (4:1)
  12. concentrationthe eluate was concentrated to dryness under reduced pressure
  13. customthe residue was recrystallized with methanol

Sources & evidence

ORD record
ord-ebe5572ba4b7417cb7e301260b746202
Source dataset
uspto-grants-1992_08
Patent number
US05142031

Reaction notes

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