Reaction #4360

Reaction equation

diethyl malonate

magnesium

2,4-dichloro-5-fluoro-3-nitro-benzoyl chloride

hydrogen

sulphuric acid

→

diethyl (2,4-dichloro-5-fluoro-3-nitro-benzoyl)-malonate

Yield 91.0%

Solvents

toluene

ethanol

ethanol

toluene

water

Conditions

Workup

1. 1
   workup.ADDITIONis added dropwise at 50°-60° C
2. 2
   Temperatureis cooled to -5° to -10° C.
3. 3
   workup.STIRRINGThereafter, the mixture is stirred at 0° C. for 1 hour
4. 4
   workup.WAITbrought to room temperature overnight
5. 5
   Temperaturewarmed at 40°-50° C. for a further 2 hours
6. 6
   workup.ADDITIONis added to the reaction mixture
7. 7
   Temperaturewhile cooling with ice
8. 8
   Otherthe organic phase is separated off
9. 9
   ExtractionThe aqueous phase is extracted with toluene
10. 10
    Extractionthe combined organic extract
11. 11
    Washis washed with saturated sodium chloride solution
12. 12
    Dryingdried with sodium sulphate

Procedure

2.1 g of carbon tetrachloride are added to 10.1 g of magnesium filings in 21 ml of ethanol and, when the evolution of hydrogen has started, a mixture of 66.6 g of diethyl malonate, 40 ml of ethanol and 150 ml of toluene is added dropwise at 50°-60° C. The mixture is subsequently stirred at this temperature for 1 hour and is cooled to -5° to -10° C. and a solution of 109.2 g of 2,4-dichloro-5-fluoro-3-nitro-benzoyl chloride in 50 ml of toluene is slowly added dropwise. Thereafter, the mixture is stirred at 0° C. for 1 hour, brought to room temperature overnight and warmed at 40°-50° C. for a further 2 hours. A mixture of 160 ml of water and 10.4 ml of concentrated sulphuric acid is added to the reaction mixture, while cooling with ice, and the organic phase is separated off. The aqueous phase is extracted with toluene, the combined organic extract is washed with saturated sodium chloride solution and dried with sodium sulphate and the solvent is stripped off. 144.5 g of diethyl (2,4-dichloro-5-fluoro-3-nitro-benzoyl)-malonate are obtained as a crude product. This is heated under reflux for 3 hours, after addition of 200 ml of water and 0.6 g of 4-toluenesulphonic acid, and the mixture is extracted with methylene chloride and dried with sodium sulphate and the solvent distilled off in vacuo. 118 g of substituted benzoylacetic acid ester are obtained as a crude product. The product is of sufficient purity for the subsequent reactions.

Source