Thionyl Chloride → 2-Chloro-3-fluoro-7-methoxyquinoline

HRID 1791657Notes

Reaction equation

HRID 1791657 reaction equation
[F:1][C:2]1[C:3](=O)[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([O:12][CH3:13])[CH:6]=2.S(Cl)([Cl:17])=O>CN(C=O)C>[Cl:17][C:3]1[C:2]([F:1])=[CH:11][C:10]2[C:5](=[CH:6][C:7]([O:12][CH3:13])=[CH:8][CH:9]=2)[N:4]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 152605803-fluoro-7-methoxyquinolin-2(1H)-one

Product 1

HCID 220305912-Chloro-3-fluoro-7-methoxyquinolineYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

3-Fluoro-7-methoxyquinol-2(1H)-one (300 mg, 1.55 mmol), (prepared as in Tetrahedron, Vol. 52, No. 9, pp. 3223–3228, 1996), was dissolved in thionyl chloride (3 ml), treated with DMF (1 drop) and heated at reflux for 1 hour. The excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene (3×). The residue was basified to pH8 with saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate (3×20 ml). The organic solution was washed with water and brine then dried (MgSO4) and evaporated to dryness to give 2-chloro-3-fluoro-7-methoxyquinoline (320 mg, 97%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 1 hour
  3. customThe excess thionyl chloride was removed by evaporation
  4. customthe residue azeotroped with toluene (3×)
  5. extractionextracted with ethyl acetate (3×20 ml)
  6. washThe organic solution was washed with water and brine
  7. dry with materialthen dried (MgSO4)
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-e66ac03e03f84c75ad3ea3256f26e11f
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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