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

HRID 2104412Notes

Reaction equation

HRID 2104412 reaction equation
[C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([O-:5])=O.[K+].[Cl-].[Mg+2].[Cl-].[Cl:14][C:15]1[CH:23]=[CH:22][C:18](C(O)=O)=[CH:17][CH:16]=1.S(Cl)(Cl)=O>C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O.C1(C)C=CC=CC=1>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][C:3]([C:18]1[CH:22]=[CH:23][C:15]([Cl:14])=[CH:16][CH:17]=1)=[O:5])[CH3:9]

Participants

9

Reactant 4

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

Product 1

HCID 101336Ethyl 3-(4-chlorophenyl)-3-oxopropanoateYield 88.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of potassium ethyl malonate (8.2 g) in ethyl acetate (100 mL), triethylamine (17 mL) and magnesium chloride (5.5 g) were added under ice cooling. The temperature of the resultant mixture was returned gradually to room temperature, and the mixture was stirred for 18 hours. In addition, a suspension of 4-chlorobenzoic acid (5.0 g), thionyl chloride (12 mL), N,N-dimethylformamide (1 drop), and toluene (100 mL) was heated under reflux for 1 hour, and the reaction mixture was concentrated. The residue was dissolved in ethyl acetate, and the solution was added dropwise to the above mixture under ice cooling. The temperature of the mixture was gradually returned to room temperature, and the mixture was stirred for 18 hours. 10% Aqueous citric acid was added to the reaction mixture, and the mixture was stirred for 30 minutes, and the organic layer was partitioned. The resultant organic layer was washed with saturated brine, followed by drying over sodium sulfate anhydrate. The solvent was distilled away under reduced pressure. The residue was separated and purified by silica gel column chromatography (chloroform), to thereby give the title compound (6.4 g).

Workup

  1. additionwere added under ice cooling
  2. customwas returned gradually to room temperature
  3. temperaturewas heated
  4. temperatureunder reflux for 1 hour
  5. concentrationthe reaction mixture was concentrated
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. additionthe solution was added dropwise to the above mixture under ice cooling
  8. customwas gradually returned to room temperature
  9. stirringthe mixture was stirred for 18 hours
  10. addition10% Aqueous citric acid was added to the reaction mixture
  11. stirringthe mixture was stirred for 30 minutes
  12. customthe organic layer was partitioned
  13. washThe resultant organic layer was washed with saturated brine
  14. dry with materialby drying over sodium sulfate anhydrate
  15. distillationThe solvent was distilled away under reduced pressure
  16. customThe residue was separated
  17. custompurified by silica gel column chromatography (chloroform)

Sources & evidence

ORD record
ord-ce27195364f345a8a4d120171ee25305
Source dataset
uspto-grants-2009_08
Patent number
US07576135B2

Reaction notes

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