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

HRID 1762259Notes

Reaction equation

HRID 1762259 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+]>CS(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 88%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

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 60 ml of dimethyl sulfoxide 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 +40° C. The resultant nitrogen is removed from the reactor through the reflux condenser. Gas evolution ceases after 4 hours at +40° 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 three times with methylene chloride. The combined organic phases are washed with water, dried over sodium sulfate and filtered through silica gel. The solution is separated by distillation, affording 36.5 g (88% 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. addition150 ml of methylene chloride are added to the reaction mixture which
  5. additionis then poured into ice water
  6. customThe organic phase is separated
  7. extractionthe aqueous phase is extracted three times with methylene chloride
  8. washThe combined organic phases are washed with water
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered through silica gel
  11. customThe solution is separated by distillation

Sources & evidence

ORD record
ord-f4a84abd94f54c0dad955b49b4951c23
Source dataset
uspto-grants-1989_05
Patent number
US04831148

Reaction notes

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