Phosphorus oxychloride → 4-chloro-6,8-difluoroquinoline

HRID 1042786Notes

Reaction equation

HRID 1042786 reaction equation
O[C:2]1[C:11]2[C:6](=[C:7]([F:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:16]>>[Cl:16][C:2]1[C:11]2[C:6](=[C:7]([F:13])[CH:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178516459HCID 178516459, compound

Product 1

HCID 27365024-chloro-6,8-difluoroquinoline

Procedure

(4-Hydroxy-6,8-difluoro-quinoline, 29.1 g, 0.160 mol) was dissolved in POCl3 (183 mL) and heated at reflux for 12 h. On complete consumption of starting material (tlc) the contents were brought to RT and excess POCl3 was removed under reduced pressure. Crude mass was azeotroped with toluene and product was diluted with ethyl acetate, organics were washed with sodium bicarbonate and solvent removed under reduced pressure. Crude product was purified by column chromatography at 100-200 mesh size silica in 0-2% EtOAc-hexane. Mass: 199.99 (M+1).

Workup

  1. temperatureheated
  2. temperatureat reflux for 12 h
  3. customOn complete consumption of starting material (tlc) the contents
  4. customwere brought to RT
  5. customexcess POCl3 was removed under reduced pressure
  6. customCrude mass was azeotroped with toluene and product
  7. additionwas diluted with ethyl acetate
  8. washorganics were washed with sodium bicarbonate and solvent
  9. customremoved under reduced pressure
  10. customCrude product was purified by column chromatography at 100-200 mesh size silica in 0-2% EtOAc-hexane

Sources & evidence

ORD record
ord-206ded171beb463db6dad648503d761a
Source dataset
uspto-grants-2013_10
Patent number
US08557816B2

Reaction notes

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