Hydrofluoric Acid → 5-Chloro-2,3-difluoropyridine

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Reaction Conditions

Reaction Steps

A 500 ml polytetrafluoroethylene reactor equipped with stirrer, thermometer and reflux condenser is charged with 120 g of hydrogen fluoride. A solution of 40.7 g (0.25 mol) of 3-amino-2,5-dichloropyridine in 100 ml of sulfolane is added dropwise at a temperature in the range from 0° C. to +10° C. Then 20.7 g (0.3 mol) of sodium nitrite are introduced into this solution at +50° C. The resultant nitrogen is removed from the reactor through reflux condenser. Gas evolution ceases after 2 hours at +50° C. 150 ml of methylene chloride are added to the reaction mixture which is then poured into ice water. The two-phase mixture is neutralised with ammonia solution. The organic phase is separated and dried over sodium sulfate. The solvent is distilled off and then 200 ml of sulfolane, 166 g (2.879 mol) of potassium fluoride and 2 g of tetrabutylammonium bromide are added to the mixture of sulfolane and the product. This reacton mixture is stirred for 7 hours at 179° C. The product is subsequently distilled off directly from the sulfolane solution. The crude product is purified by distillation, affording the 5-chloro-2,3-difluoropyridine, b.p. 137°-139° C.

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