Methyl acetoacetate → 2-(4-Fluorophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one

HRID 1993920Notes

Reaction equation

C[O:2][C:3](=O)[CH2:4][C:5](=O)[CH3:6].[F:9][C:10]1[CH:15]=[CH:14][C:13]([NH:16][NH2:17])=[CH:12][CH:11]=1>C(O)(=O)C>[F:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[C:3](=[O:2])[CH2:4][C:5]([CH3:6])=[N:17]2)=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 3-oxo-butyric acid methyl ester (2.8 g) in acetic acid (6.5 mL) in a round bottom flask under argon was added 4-fluorophenylhydrazine (3.05 g). The mixture was immersed into an oil bath and heated to 120° C. overnight. The reaction vessel was then cooled and the acetic acid was evaporated in vacuo and the remaining solid was dissolved in EtOAc and water. The phases were separated and the aqueous phase was extracted with further EtOAc. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo and azeotroped with toluene (2×). The crude residue was then purified via ISCO Combiflash chromatography using EtOAc/heptane as eluent to afford the desired 2-(4-fluoro-phenyl)-5-methyl-2,4-dihydro-pyrazol-3-one (3.2 g) as a beige solid. MS (ESI+): 193.3 ([M+H]+).

Workup

customThe mixture was immersed into an oil bath
temperatureThe reaction vessel was then cooled
customthe acetic acid was evaporated in vacuo
dissolutionthe remaining solid was dissolved in EtOAc
customThe phases were separated
extractionthe aqueous phase was extracted with further EtOAc
washThe combined organic phases were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated in vacuo
customazeotroped with toluene (2×)
customThe crude residue was then purified via ISCO Combiflash chromatography

Sources & evidence

ORD record: ord-ae81aad7aa3a43cda218959f81178884
Source dataset: uspto-grants-2010_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07652057B2

Reaction notes

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