Sulfuric Acid → Diethyl 2-chloro-3,5-difluoro-4-methylbenzoyl-malonate

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Reaction Steps

4.5 g of magnesium chips are suspended in 10 ml of anhydrous ethanol. 1 ml of carbon tetrachloride is added and, when the reaction has started, a mixture of 29.7 g of diethyl malonate, 20 ml of absolute ethanol and 80 ml of anhydrous toluene is added dropwise at 50°-60° C. The mixture is then heated at 50°-60° C. for a further hour and cooled to -5° C. to -10° C. with dry ice/acetone and a solution of 41.7 g of 2-chloro-3,5-difluoro-4-methylbenzoyl chloride in 20 ml of absolute toluene is slowly added dropwise at this temperature. The mixture is stirred at 0° to -5° C. for 1 hour and left to come to room temperature overnight, and a mixture of 80 ml of ice-water and 12 ml of concentrated sulphuric acid is allowed to run in, while cooling with ice. The phases are separated and subsequently extracted twice with toluene. The combined toluene solutions are washed with saturated NaCl solution and dried with Na2SO4 and the solvent is stripped off in vacuo. 65.1 g of diethyl 2-chloro-3,5-difluoro-4-methylbenzoyl-malonate are obtained as a crude product.

Provenance & Evidence