Hydrofluoric Acid → 2,5-Dichloro-3-fluoropyridine

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Reaction Steps

A 500 ml polytetrafluoroethylene reactor equipped with stirrer, thermometer and reflux condenser is charged with 60 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 the 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 concentrated ammonia solution. The organic phase is separated and the aqueous phase is extracted several times with methylene chloride. The combined organic phase are dried over sodium sulfate and concentrated by evaporation. The solution of the sulfolane product is separated by distillation, affording 34.3 g (82.6% of theory) of 2,5-dichloro-3-fluoropyridine.

Provenance & Evidence