Sulfuric Acid → Ethyl 2,4-difluoro-3-methyl-β-oxobenzenepropanoate

HRID 1381996Notes

Reaction equation

HRID 1381996 reaction equation
[Mg].[C:2]([O:8][CH2:9][CH3:10])(=[O:7])[CH2:3][C:4]([O-:6])=O.[F:11][C:12]1[C:20]([CH3:21])=[C:19]([F:22])[CH:18]=[CH:17][C:13]=1C(Cl)=O.OS(O)(=O)=O>C1(C)C=CC=CC=1.O.C(O)C.C(Cl)(Cl)(Cl)Cl>[F:11][C:12]1[C:20]([CH3:21])=[C:19]([F:22])[CH:18]=[CH:17][C:13]=1[C:4]([CH2:3][C:2]([O:8][CH2:9][CH3:10])=[O:7])=[O:6]

Participants

9

Reactant 4

HCID 1118Sulfuric AcidHCID 3595298Propanedioic acid, monoethyl esterHCID 5462224MagnesiumHCID 121374872,4-Difluoro-3-methylbenzoyl chloride

Product 1

HCID 54282296Ethyl 2,4-difluoro-3-methyl-β-oxobenzenepropanoate

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 5943Carbon TetrachlorideSolvent

Procedure

8 ml of ethnol and 1 ml of carbon tetrachloride are added to 3.6 g of magnesium turnings. After initiation of the reaction, a mixture of 22.2 g of ethyl malonate, 15 ml of ethanol and 60 ml of toluene are added at 50° C. The mixture is warmed for 1 hour at 50°-60° C. and then cooled to -5°--10° C. A solution of 25.7 g of 2,4-difluoro-3-methyl-benzoyl chloride (from 2,4-difluoro-3-methylbenzoic acid and thionyl chloride) in 15 ml of toluene is added dropwise at this temperature. The mixture is then allowed to come to room temperature. After standing overnight, a mixture of 60 ml of water and 10 ml of H2SO4 is added dropwise. The phases are separated, and the organic phase is washed with water, dried and concentrated. 50 ml of water and 2.0 g of p-toluenesulphonic acid are added to the oily residue. The mixture is refluxed for 4.5 hours, the phases are separated, and the organic phase is dried and concentrated in vacuo. 33.9 g of the title compound remain as a crude oil.

Workup

  1. customAfter initiation of the reaction
  2. additionare added at 50° C
  3. temperatureThe mixture is warmed for 1 hour at 50°-60° C.
  4. temperaturecooled to -5°--10° C
  5. customto come to room temperature
  6. additionis added dropwise
  7. customThe phases are separated
  8. washthe organic phase is washed with water
  9. customdried
  10. concentrationconcentrated
  11. addition50 ml of water and 2.0 g of p-toluenesulphonic acid are added to the oily residue
  12. temperatureThe mixture is refluxed for 4.5 hours
  13. customthe phases are separated
  14. customthe organic phase is dried
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-05084e2ffa5a45e996fc8d793c1e41a4
Source dataset
uspto-grants-1989_02
Patent number
US04804760

Reaction notes

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