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

Temperature

179 °C

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.

1. customA 500 ml polytetrafluoroethylene reactor equipped with stirrer
2. temperaturethermometer and reflux condenser
3. customThe resultant nitrogen is removed from the reactor
4. temperaturethrough reflux condenser
5. addition150 ml of methylene chloride are added to the reaction mixture which
6. additionis then poured into ice water
7. customThe organic phase is separated
8. dry with materialdried over sodium sulfate
9. distillationThe solvent is distilled off
10. distillationThe product is subsequently distilled off directly from the sulfolane solution
11. distillationThe crude product is purified by distillation

ORD record

ord-40ed53e3ff17442e8265b89f9fa8d20d

Source dataset

uspto-grants-1989_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04831148