Phosphorus oxychloride → 2-Chloro-1,5-naphthyridine

HRID 707446Notes

Reaction equation

HRID 707446 reaction equation
[NH:1]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]1=O.P(Cl)(Cl)([Cl:14])=O>>[Cl:14][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][N:6]=2)[N:1]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 5896801,5-Naphthyridin-2-ol

Product 1

HCID 151530312-Chloro-1,5-naphthyridine

Conditions

Temperature
100 °C

Procedure

A 250 mL round bottomed flask charged with 1,5-naphthyridin-2(1H)-one (2.98 g, 20.37 mmol) and phosphorus oxychloride (40 ml, 437 mmol) was heated at 100° C. for 3 h. The reaction was cooled to room temperature and excess POCl3 was removed in vacuo. The residue was poured onto ice and neutralized with NaHCO3. The mixture was extracted with DCM (4×) and the combined organic layers were evaporated onto silica gel and purified by flash chromatography (ISCO (80 gram)) eluting with EtOAc:DCM (0:1→1:4) to give 1.08 g (32%, 2 steps) of a light-yellow amorphous solid. ESI-MS 164.9, 166.9 [M+1].

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customexcess POCl3 was removed in vacuo
  3. additionThe residue was poured onto ice and neutralized with NaHCO3
  4. extractionThe mixture was extracted with DCM (4×)
  5. customthe combined organic layers were evaporated onto silica gel
  6. custompurified by flash chromatography (ISCO (80 gram))
  7. washeluting with EtOAc:DCM (0:1→1:4)
  8. customto give 1.08 g (32%, 2 steps) of a light-yellow amorphous solid

Sources & evidence

ORD record
ord-86f2b729bf554514bf026e2f4267f144
Source dataset
uspto-grants-2015_11
Patent number
US09174992B2

Reaction notes

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