Sulfuric Acid → Diethyl 2-(2,4-dichloro-5-fluorobenzoyl)malonate

HRID 637922Notes

Reaction equation

HRID 637922 reaction equation
[Mg].[C:2]([O:10][CH2:11][CH3:12])(=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C(=O)=O.CC(C)=O.[Cl:20][C:21]1[CH:29]=[C:28]([Cl:30])[C:27]([F:31])=[CH:26][C:22]=1[C:23](Cl)=[O:24].S(=O)(=O)(O)O>C(O)C.CCOCC.C(Cl)(Cl)(Cl)Cl>[Cl:20][C:21]1[CH:29]=[C:28]([Cl:30])[C:27]([F:31])=[CH:26][C:22]=1[C:23]([CH:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:2]([O:10][CH2:11][CH3:12])=[O:9])=[O:24]

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 7761Diethyl MalonateHCID 27368212,4-Dichloro-5-fluorobenzoyl chlorideHCID 5462224MagnesiumHCID 18522661Acetone cardice

Product 1

HCID 13326819Diethyl 2-(2,4-dichloro-5-fluorobenzoyl)malonateYield 99.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 3283Diethyl EtherSolvent2×HCID 5943Carbon TetrachlorideSolvent

Procedure

24.3 g of magnesium turnings are suspended in 50 ml of anhydrous ethanol. 5 ml of carbon tetrachloride are added, and, when the reaction has started, a mixture of 160 g of diethyl malonate, 100 ml of absolute ethanol and 400 ml of anhydrous ether is added dropwise, vigorous refluxing taking place. After the reaction has died down, the mixture is heated at the boil for a further 2 hours and cooled to -5° C. to -10° C. with dry ice/acetone, and a solution of 227.5 g of 2,4-dichloro-5-fluoro-benzoyl chloride (1) in 100 ml of absolute ether is slowly added dropwise at this temperature. The mixture is stirred for 1 hour at 0° C. to -5° C., and is allowed to reach room temperature overnight, and a mixture of 400 ml of ice water and 25 ml of concentrated sulphuric acid is allowed to run in, while cooling with ice. The phases are separated, and further extracted twice with ether. The combined ether solutions are washed with saturated NaCl solution and dried with Na2SO4, and the solvent is stripped off in vacuo. 349.5 g of diethyl 2,4-dichloro-5-fluoro-benzoyl-malonate (3) are obtained as a crude product.

Workup

  1. additionis added dropwise
  2. temperaturevigorous refluxing
  3. temperaturethe mixture is heated at the boil for a further 2 hours
  4. waitto reach room temperature overnight
  5. temperaturewhile cooling with ice
  6. customThe phases are separated
  7. extractionfurther extracted twice with ether
  8. washThe combined ether solutions are washed with saturated NaCl solution
  9. dry with materialdried with Na2SO4

Sources & evidence

ORD record
ord-ee8d2da4929047a6893b7ca9412c6c13
Source dataset
uspto-grants-1985_12
Patent number
US04559341

Reaction notes

Loading…