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

HRID 454132Notes

Reaction equation

HRID 454132 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-b0315f4f00794cdf8cf97696b2319539
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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