Trifluoroacetic acid → Methyl 4-formyl-3-hydroxybenzoate

HRID 1820935Notes

Reaction equation

HRID 1820935 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].FC(F)(F)[C:14](O)=[O:15]>>[CH:14]([C:3]1[C:2]([OH:1])=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6])=[O:15].[CH:14]([C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[OH:1])=[O:15]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 88068Methyl 3-Hydroxybenzoate

Product 2

HCID 14395860Methyl 4-formyl-3-hydroxybenzoateHCID 14774772Methyl 2-formyl-3-hydroxybenzoate

Procedure

Methyl 3-hydroxybenzoate (75.5 g) is dissolved in trifluoroacetic acid (2 L), thereto is added hexamethylene-tetramine tetramine (141.4 g) at room temperature, and the mixture is heated under reflux for 3 hours. The reaction solution is concentrated under reduced pressure and water is added to the resulting residue. The mixture is adjusted to pH 8 with potassium carbonate and sodium hydrogen carbonate, diluted with water and extracted with ethyl acetate. The organic layer is washed with saturated brine, dried over sodium sulfate, and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: hexane/ethyl acetate=8/1, 5/1, and then 2/1) to give methyl 2-formyl-3-hydroxybenzoate (54.6 g) (ESI-MS m/z: 179[M−H]−) and methyl 4-formyl-3-hydroxybenzoate (4.4 g) (ESI-MS m/z: 179[M−H]−).

Workup

  1. temperaturethe mixture is heated
  2. temperatureunder reflux for 3 hours
  3. concentrationThe reaction solution is concentrated under reduced pressure and water
  4. additionis added to the resulting residue
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. washThe organic layer is washed with saturated brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customto remove the solvent under reduced pressure
  11. customThe resulting residue is purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-2723e5296e8c422fad0b6e82632c5d71
Source dataset
uspto-grants-2009_10
Patent number
US07605158B2

Reaction notes

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