Phosphorus oxychloride → 4-Chloro-7-methoxy-8-methylquinoline

HRID 402149Notes

Reaction equation

HRID 402149 reaction equation
O[C:2]1[C:11]2[C:6](=[C:7]([CH3:14])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:2]1[C:11]2[C:6](=[C:7]([CH3:14])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1784877164-Hydroxy-7-methoxy-8-methyl-quinoline

Product 1

HCID 211019544-Chloro-7-methoxy-8-methylquinolineYield 92.6%

Procedure

A solution of 4-hydroxy-7-methoxy-8-methylquinoline (59, 6.4 g, 33.8 mmol) in POCl3 (17.2 g, 111.6 mmol) was heated at reflux for 1 h under nitrogen. Then, the resulting solution was cooled down to room temperature and the excess of POCl3 was evaporated under reduced pressure. The residue was partitioned between ice-cold 1N NaOH and AcOEt. The organic layer was dried (Na2SO4), and evaporated. The residue was purified by silica-gel filtration (AcOEt/CH2Cl2/Heptane, 4:4:2) to give 6.5 g (92.5%) of the target product 60 as yellow needles: m/z=208 (M+H)+.

Workup

  1. temperatureat reflux for 1 h under nitrogen
  2. customthe excess of POCl3 was evaporated under reduced pressure
  3. customThe residue was partitioned between ice-cold 1N NaOH and AcOEt
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated
  6. filtrationThe residue was purified by silica-gel filtration (AcOEt/CH2Cl2/Heptane, 4:4:2)

Sources & evidence

ORD record
ord-31aa572ffbca479c9015b204b8eca2f5
Source dataset
uspto-grants-2014_06
Patent number
US08741926B2

Reaction notes

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