Phosphorus oxychloride → 4-Chloro-1,5-naphthyridine

HRID 869451Notes

Reaction equation

HRID 869451 reaction equation
C(O)(=O)C.[N:5]1[C:14]2[C:9](=[N:10][CH:11]=[CH:12][CH:13]=2)[C:8](O)=[CH:7][CH:6]=1.O=P(Cl)(Cl)[Cl:18]>>[Cl:18][C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][N:10]=2)[N:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178476732HCID 178476732, compound

Product 1

HCID 5962624-Chloro-1,5-naphthyridine

Conditions

Temperature
110 °C

Procedure

A mixture of 1,5-naphthyridin-4-ol acetic acid salt (D-6) (800 mg, 3.0 mmol, 1.0 eq) in phosphoroxychloride (5 mL, 53 mol, 17.6 eq) is stirred at 110° C. for 30 min, cooled to RT and then concentrated in vacuo. The residue is poured into ice-water (50 mL) and neutralized with saturated aqueous NaHCO3 solution to adjust the pH to 8-9 while keeping the temperature below 5° C. The mixture is stirred at RT for 30 min and then extracted with DCM (3×40 mL). The combined organic layers are washed with brine, dried over Na3SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash column chromatography on silica gel (1-2% MeOH-DCM) to afford the product, 4-chloro-1,5-naphthyridine (D-7).

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated in vacuo
  3. additionThe residue is poured into ice-water (50 mL)
  4. customthe temperature below 5° C
  5. stirringThe mixture is stirred at RT for 30 min
  6. extractionextracted with DCM (3×40 mL)
  7. washThe combined organic layers are washed with brine
  8. dry with materialdried over Na3SO4
  9. filtrationfiltered
  10. concentrationThe filtrate is concentrated in vacuo
  11. customthe residue is purified by flash column chromatography on silica gel (1-2% MeOH-DCM)

Sources & evidence

ORD record
ord-b963e618680c448bb24a76bff36e5ace
Source dataset
uspto-grants-2015_03
Patent number
US08969363B2

Reaction notes

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