Phosphorus oxychloride → 8-Bromo-4-chloroquinoline

HRID 1403095Notes

Reaction equation

HRID 1403095 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Br:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[NH:15][CH:14]=[CH:13][C:12]2=O>>[Br:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[C:12]2[Cl:3]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 124036828-Bromo-1,4-dihydroquinolin-4-one

Product 1

HCID 124036918-Bromo-4-chloroquinoline

Procedure

A suspension of 2-bromoaniline (20.9 g) and 5-(methoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione (22.6 g) in 2-propanol (240 ml) was heated to reflux for 1 hour. The reaction solution was cooled to 0° C., and the deposit was then filtrated to obtain a pale yellow solid (35.0 g). A suspension of the obtained pale yellow solid (10.0 g) in Dowtherm (100 ml) was heated at 210° C. for 1 hour. After cooling, hexane (100 ml) was added to the reaction solution, and the deposit was filtrated to obtain 8-bromoquinolin-4(1H)-one (6.3 g). Phosphorus oxychloride (5.9 ml) was added to 8-bromoquinolin-4(1H)-one (9 g), and the mixture was heated to reflux for 2 hours. The solvent was distilled off under reduced pressure, and chloroform was added to the residue. The reaction solution was neutralized with an aqueous sodium hydroxide solution with cooling in an ice bath and partitioned into organic and aqueous layers. The organic layer was washed with brine. The organic layer thus washed was dried over anhydrous sodium sulfate. Then, the solvent was distilled off, and the residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain 8-bromo-4-chloroquinoline (8.3 g) as a white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 hours
  3. distillationThe solvent was distilled off under reduced pressure, and chloroform
  4. additionwas added to the residue
  5. temperaturewith cooling in an ice bath
  6. custompartitioned into organic and aqueous layers
  7. washThe organic layer was washed with brine
  8. washThe organic layer thus washed
  9. dry with materialwas dried over anhydrous sodium sulfate
  10. distillationThen, the solvent was distilled off
  11. customthe residue was purified by neutral silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record
ord-f4030206459a410ba87987cf37bb27da
Source dataset
uspto-grants-2014_12
Patent number
US08912181B2

Reaction notes

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