Hydrochloric Acid → 6-Fluoro-3-(4-hydroxyphenoxy)-2-pyrazinecarbonitrile

HRID 392368Notes

Reaction equation

HRID 392368 reaction equation
F[C:2]1[C:3]([C:9]#[N:10])=[N:4][C:5]([F:8])=[CH:6][N:7]=1.[C:11]1([CH:18]=[CH:17][C:15]([OH:16])=[CH:14][CH:13]=1)[OH:12].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O.O.C(OCC)(=O)C>[F:8][C:5]1[N:4]=[C:3]([C:9]#[N:10])[C:2]([O:12][C:11]2[CH:18]=[CH:17][C:15]([OH:16])=[CH:14][CH:13]=2)=[N:7][CH:6]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 785HydroquinoneHCID 11430Potassium CarbonateHCID 226628293,6-Difluoropyrazine-2-carbonitrile

Product 1

HCID 226628546-Fluoro-3-(4-hydroxyphenoxy)-2-pyrazinecarbonitrileYield 15.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 30 mL of dimethylformamide was dissolved 3.0 g of 3,6-difluoro-2-pyrazinecarbonitrile. Then, 2.6 g of hydroquinone, followed by 6.5 g of potassium carbonate, was added at an ice-cooled temperature, and the mixture thus obtained was stirred at room temperature for 15 minutes. A mixture of 30 mL of ethyl acetate and 60 ml of water was added to the reaction mixture, pH was adjusted to 5 with 6 mol/L hydrochloric acid, and the organic layer was separated. The organic layer thus obtained was washed successively with water and saturated aqueous solution of sodium chloride and dried on anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=3:1] to obtain 0.75 g of 6-fluoro-3-(4-hydroxyphenoxy)-2-pyrazinecarbonitrile as a yellow-colored solid product.

Workup

  1. temperaturecooled temperature
  2. customthe mixture thus obtained
  3. additionwas added to the reaction mixture, pH
  4. customthe organic layer was separated
  5. customThe organic layer thus obtained
  6. washwas washed successively with water and saturated aqueous solution of sodium chloride
  7. dry with materialdried on anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by silica gel column chromatography [eluent: n-hexane:ethyl acetate=3:1]

Sources & evidence

ORD record
ord-3adbcfdfd8a749059c96b34351cb8651
Source dataset
uspto-grants-2004_10
Patent number
US06800629B2

Reaction notes

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