Phosphorus oxychloride → 6-Chloropyrimidine-4-carbonitrile

HRID 2401178Notes

Reaction equation

HRID 2401178 reaction equation
O[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH2:10])=O)[CH:3]=1.P(Cl)(Cl)([Cl:13])=O>>[Cl:13][C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]#[N:10])[CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178513697HCID 178513697, compound2×

Product 1

HCID 224988816-Chloropyrimidine-4-carbonitrileYield 61.2%

Procedure

6-Hydroxy-4-pyrimidinecarboxamide (Intermediate 7, 563 mg, 4.05 mmol) was taken up in phosphorus oxychloride (3.9 mL, 41.8 mmol) and the resulting mixture was heated under reflux for 18 hours. The reaction mixture was allowed to cool to room temperature and evaporated under reduced pressure. The residue was poured into ice cooled water, neutralised with 0.88 ammonia solution and extracted with ethyl acetate (×3). The ethyl acetate layers were combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-20% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil (346 mg);

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureunder reflux for 18 hours
  3. customevaporated under reduced pressure
  4. additionThe residue was poured into ice
  5. temperaturecooled water
  6. extractionextracted with ethyl acetate (×3)
  7. customdried under magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by column chromatography (Biotage SP4)
  10. washeluting with a gradient of 0-20% ethyl acetate and iso-hexane
  11. additionProduct containing fractions
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-171ed7a9457442bab458fdebf41c9160
Source dataset
uspto-grants-2014_08
Patent number
US08796283B2

Reaction notes

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