Trifluoroacetic acid → Methyl 4-formyl-3-hydroxybenzoate

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Reaction Steps

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]−).

Provenance & Evidence