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

HRID 1762262Notes

Reaction equation

HRID 1762262 reaction equation
[FH:1].N[C:3]1[C:4]([Cl:10])=[N:5][CH:6]=[C:7]([Cl:9])[CH:8]=1.N([O-])=O.[Na+]>CC(N(C)C)=O>[Cl:10][C:4]1[C:3]([F:1])=[CH:8][C:7]([Cl:9])=[CH:6][N:5]=1

Participants

5

Reactant 3

HCID 14917Hydrofluoric AcidHCID 27999993-Amino-2,5-dichloropyridineHCID 23668193Sodium Nitrite

Product 1

HCID 109648772,5-Dichloro-3-fluoropyridineYield 87.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

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 dimethylacetamide is added dropwise at a temperature in the range from 0° to +10° C. Then 20.7 g (0.3 mol) of sodium nitrite are introduced into this solution at 55° C. The resultant nitrogen is removed from the reactor through the reflux condenser. Gas evolution ceases after 21/2 hours at 55° 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 phases are dried over sodium sulfate and concentrated by evaporation. The crude product is purified by distillation, affording 36.4 g (87.8% of theory) of 2,5-dichloro-3 -fluoropyridine.

Workup

  1. customA 500 ml polytetrafluoroethylene reactor equipped with stirrer
  2. temperaturethermometer and reflux condenser
  3. customThe resultant nitrogen is removed from the reactor through the reflux condenser
  4. custom2 hours
  5. customat 55° C
  6. addition150 ml of methylene chloride are added to the reaction mixture which
  7. additionis then poured into ice water
  8. customThe organic phase is separated
  9. extractionthe aqueous phase is extracted several times with methylene chloride
  10. dry with materialThe combined organic phases are dried over sodium sulfate
  11. concentrationconcentrated by evaporation
  12. distillationThe crude product is purified by distillation

Sources & evidence

ORD record
ord-9a703b2bbc004dbd81c345a219049087
Source dataset
uspto-grants-1989_05
Patent number
US04831148

Reaction notes

Loading…