Hydrochloric Acid → Ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoate

HRID 2102303Notes

Reaction equation

HRID 2102303 reaction equation
[H-].[Na+].[CH3:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[CH:7]=1)=[O:5].[C:13](OCC)(=[O:19])[C:14]([O:16][CH2:17][CH3:18])=[O:15].Cl>CN(C=O)C.C(OCC)(=O)C>[CH2:17]([O:16][C:14](=[O:15])[C:13](=[O:19])[CH2:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[CH:7]=1)=[O:5])[CH3:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 149331-(3-Chlorophenyl)ethanoneHCID 24758Sodium hydride

Product 1

HCID 11054223Ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoateYield 67.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% oil dispersion, 1.24 g, 31.1 mmol) was added in portions to a solution of 3-chloroacetophenone (4.0 g, 25.9 mmol) and diethyl oxalate (4.54 g, 31.1 mmol) in DMF (32 ml) at 0° C. The mixture stirred at room temperature for 1 h and was then heated at 80° C. for a half an h. After cooling, the mixture was treated with 3N HCl and then diluted with ethyl acetate. The organic layer was washed with water (3X) and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was then purified by flash column chromatography on silica using 0-10% ethyl acetate in hexanes to afford of 4-(3-chloro-phenyl)-2,4-dioxo-butyric acid ethyl ester (4.43 g, 67%, yellow solid). 1H NMR (CDCl3) d (ppm): 15.12 (br s, 1H), 7.98 (s, 1H), 7.88 (d, 1H), 7.58 (d, 1H), 7.47 (t, 1H), 7.05 (s, 1H), 4.39 (m, 2H), 1.41 (m, 3H).

Workup

  1. temperaturewas then heated at 80° C. for a half an h
  2. temperatureAfter cooling
  3. washThe organic layer was washed with water (3X) and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was then purified by flash column chromatography on silica using 0-10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-862c717c1904493d8519bac89f88f415
Source dataset
uspto-grants-2009_08
Patent number
US07576077B2

Reaction notes

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