Citric Acid → Ethyl 3-(4-chlorophenyl)-3-oxopropanoate

HRID 902885Notes

Reaction equation

HRID 902885 reaction equation
[Cl-].[Mg+2].[Cl-].[C:4]([O:10][CH2:11][CH3:12])(=[O:9])[CH2:5][C:6]([O-:8])=O.[K+].[Cl:14][C:15]1[CH:23]=[CH:22][C:18](C(O)=O)=[CH:17][CH:16]=1.S(Cl)(Cl)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(OCC)(=O)C.CN(C)C=O.C1(C)C=CC=CC=1.C(N(CC)CC)C>[Cl:14][C:15]1[CH:23]=[CH:22][C:18]([C:6](=[O:8])[CH2:5][C:4]([O:10][CH2:11][CH3:12])=[O:9])=[CH:17][CH:16]=1

Participants

10

Reactant 5

HCID 311Citric AcidHCID 63184-Chlorobenzoic AcidHCID 24386Thionyl ChlorideHCID 3446434Potassium ethyl malonateHCID 5360315Magnesium Chloride

Product 1

HCID 101336Ethyl 3-(4-chlorophenyl)-3-oxopropanoate

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (17 ml) and magnesium chloride (5.5 g) were added to a suspension of potassium ethyl malonate (8.2 g) in ethyl acetate (100 ml) under ice cooling, and the mixture was stirred for 18 hours while the temperature of the system was gradually raised to room temperature. On the other hand, a suspension composed of 4-chlorobenzoic acid (5.0 g), thionyl chloride (12 ml), N,N-dimethylformamide (one drop) and toluene (100 ml) was heated under reflux for 1 hour, and the reaction mixture was then concentrated. The resultant residue was dissolved in ethyl acetate, and the solution was added dropwise to the reaction mixture previously prepared under ice cooling. The resultant mixture was stirred for 18 hours while the temperature of the system was gradually raised to room temperature. A 10% aqueous solution of citric acid was added to the reaction mixture, and the mixture was stirred for 30 minutes to separate the resultant organic layer. The organic layer was washed with saturated aqueous solution of sodium chloride and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was isolated and purified by column chromatography on silica gel (chloroform) to obtain the title compound (6.4 g).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1 hour
  3. concentrationthe reaction mixture was then concentrated
  4. dissolutionThe resultant residue was dissolved in ethyl acetate
  5. additionthe solution was added dropwise to the reaction mixture
  6. custompreviously prepared under ice cooling
  7. temperaturewas gradually raised to room temperature
  8. stirringthe mixture was stirred for 30 minutes
  9. customto separate the resultant organic layer
  10. washThe organic layer was washed with saturated aqueous solution of sodium chloride
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-3d7510608176433c8c8763e375663e4a
Source dataset
uspto-grants-2008_04
Patent number
US07365205B2

Reaction notes

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