Phosphorus oxychloride → 4-Chloro-8-methoxyquinoline

HRID 574286Notes

Reaction equation

HRID 574286 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[C:8]2O.O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:8]1[C:7]2[C:12](=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][CH:6]=2)[N:11]=[CH:10][CH:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178488809HCID 178488809, compound

Product 1

HCID 123366624-Chloro-8-methoxyquinolineYield 72.3%

Procedure

Compound 16 (2.65 g, 15.1 mmol) was dissolved in POCl3 (4.2 ml, 45.3 mmol) under nitrogen atmosphere and refluxed for 2 h. It was then cooled and concentrated under vacuum. The solid concentrate was taken in a beaker with 200 ml water neutralized with NaHCO3 powder and extracted with EtOAc. The solution was dried over Na2SO4, filtered, and concentrated. This crude product was then purified through column chromatography using ethyl acetate to get 17 as brown solid (2.113 g, 72%). 1H NMR (400 MHz, CDCl3) δ ppm 4.079 (s, 3H), 7.08-7.1 (d, 1H, J=8 Hz), 7.49-7.56 (m, 2H), 7.76-7.78 (d, 1H, J=8 Hz), 8.76-8.77 (d, 1H, J=4 Hz).

Workup

  1. temperaturerefluxed for 2 h
  2. temperatureIt was then cooled
  3. concentrationconcentrated under vacuum
  4. concentrationThe solid concentrate
  5. extractionextracted with EtOAc
  6. dry with materialThe solution was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThis crude product was then purified through column chromatography

Sources & evidence

ORD record
ord-bf59bb2880d248f49203aecb27ffbc59
Source dataset
uspto-grants-2015_05
Patent number
US09034877B2

Reaction notes

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