Phosphorus oxychloride → Ethyl 4-chloro-6-methoxyquinoline-3-carboxylate

HRID 1640116Notes

Reaction equation

HRID 1640116 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]=[C:11]([C:17](OCC)=O)[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:5][CH:4]=1.O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:17]1[C:5]2[C:6](=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=[CH:10][C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 6189812-((4-Methoxy-phenylamino)-methylene)-malonic acid diethyl ester

Product 1

HCID 304558Ethyl 4-chloro-6-methoxyquinoline-3-carboxylateYield 96%

Procedure

Diethyl {[(4-methoxyphenyl)amino]methylene}malonate (63.5 g, 0.22 mol) was dissolved into POCl3 (300 mL, 3.0 mol), and the reaction mixture was heated at reflux for 16 h. After removal of solvent, toluene was added and the mixture was concentrated to remove remaining POCl3. The residue was diluted with DCM, washed with aqueous Na2CO3 and brine, dried over Na2SO4 and concentrated to give ethyl 4chloro-6methoxyquinoline-3-carboxylate (55.4 g, 96% yield) as a yellow solid which was used without further purification. LCMS: (FA) ES+ 266.1.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 16 h
  3. customAfter removal of solvent, toluene
  4. additionwas added
  5. concentrationthe mixture was concentrated
  6. customto remove
  7. additionThe residue was diluted with DCM
  8. washwashed with aqueous Na2CO3 and brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-a8e2a33a690d411d82e360bc6b2a39c6
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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