Hydrofluoric Acid → 4-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenol

HRID 845698Notes

Reaction equation

HRID 845698 reaction equation
N[C:2]1[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[FH:17].N([O-])=O.[Na+]>>[Cl:8][C:6]1[CH:7]=[C:2]([F:17])[C:3]([O:9][C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[N:4][CH:5]=1

Participants

4

Reactant 3

HCID 14917Hydrofluoric AcidHCID 201299724-(3-Amino-5-chloropyridin-2-yloxy)phenolHCID 23668193Sodium Nitrite

Product 1

HCID 155928384-((5-Chloro-3-fluoro-2-pyridinyl)oxy)phenolYield 90.2%

Conditions

Temperature
0 °C

Procedure

122.5 g (0.518 mole) of 4-(3-amino-5-chloropyridin-2-yloxy)phenol are introduced at -8° to 0° C. into a vessel charged with 400 g (20 moles) of hydrogen fluoride. Then 37.3 g (0.540 mole) of sodium nitrite are added in portions over one hour. The mixture is stirred for 2 hours at 0° C. and slowly heated to 55° C. in an autoclave. Excess hydrogen fluoride is removed by distillation and the residue is taken up in 200 ml of methylene chloride and the solution is neutralised with ice-water and ammonia, the organic phase is dried and concentrated by evaporation, affording 112 g of 4-(5-chloro-3-fluoropyridin-2-yloxy)phenol with a melting point of 97°-98° C.

Workup

  1. temperatureslowly heated to 55° C. in an autoclave
  2. customExcess hydrogen fluoride is removed by distillation
  3. customthe organic phase is dried
  4. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-757b3d1899ba4db3a80f4c34be0f9d0e
Source dataset
uspto-grants-1988_07
Patent number
US04759796

Reaction notes

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