Phosphorus oxychloride → 4-Chloro-1,6-naphthyridine

HRID 1013707Notes

Reaction equation

HRID 1013707 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[C:4](O)=[CH:3][CH:2]=1.P(Cl)(Cl)([Cl:14])=O>>[Cl:14][C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[N:7][CH:6]=2)[N:1]=[CH:2][CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178516446HCID 178516446, compound

Product 1

HCID 217666944-Chloro-1,6-naphthyridine

Procedure

1,6-naphthyridin-4-ol (0.530 g, 3.63 mmol) was dissolved in phosphorus oxychloride (4.06 ml, 43.5 mmol) and heated at reflux for 14 h. Excess POCl3 was removed under reduced pressure and the mixture was azeotroped with toluene. The resultant gum was treated with sat. NaHCO3 until no gas was generated. The mixture was extracted with EtOAc, the combined extracts were washed with sodium bicarbonate and the solvent was removed under reduced pressure. The crude product was purified via column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-90% EtOAc/DCM) to afford 4-chloro-1,6-naphthyridine as a white solid.

Workup

  1. temperatureheated
  2. temperatureat reflux for 14 h
  3. customExcess POCl3 was removed under reduced pressure
  4. customthe mixture was azeotroped with toluene
  5. additionThe resultant gum was treated with sat. NaHCO3 until no gas
  6. extractionThe mixture was extracted with EtOAc
  7. washthe combined extracts were washed with sodium bicarbonate
  8. customthe solvent was removed under reduced pressure
  9. customThe crude product was purified via column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-90% EtOAc/DCM)

Sources & evidence

ORD record
ord-46b0a16a8d4a4a3494787a0ebc44e089
Source dataset
uspto-grants-2011_07
Patent number
US07981891B2

Reaction notes

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