Methanol → Methyl p-aminosalicylate

Participants

Reaction Steps

To a stirred solution of 4-amino salicylic acid (110.0 g; 718 mmol) in dry MeOH (3025 mL) was slowly added concentrated sulfuric acid (187 mL; 3.5 mmol) via pipette at room temperature under nitrogen atmosphere. The resulting solution was heated to reflux for 20 hours then allowed to cool to room temperature. The reaction was concentrated at reduced pressure to about ¼ the original volume, then neutralized by the careful addition of saturated aqueous sodium bicarbonate to pH 7-8. The resulting precipitate was collected on a Buchner funnel with suction, washed with water, and allowed to air dry. The resulting gray solid was dissolved in EtOAc (1.5 L) and treated with decolorizing charcoal. Filtration and recrystallization (EtOAc/hexanes or MeOH/water (1:3)) provided the ester as an off white crystal (94.5 g; 79%).

Provenance & Evidence