Methanol → Methyl p-aminosalicylate

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%).

1. temperatureThe resulting solution was heated
2. temperatureto reflux for 20 hours
3. concentrationThe reaction was concentrated at reduced pressure
4. additionneutralized by the careful addition of saturated aqueous sodium bicarbonate to pH 7–8
5. customThe resulting precipitate was collected on a Buchner funnel with suction
6. washwashed with water
7. customto air dry
8. dissolutionThe resulting gray solid was dissolved in EtOAc (1.5 L)
9. additiontreated with decolorizing charcoal
10. filtrationFiltration and recrystallization (EtOAc/hexanes or MeOH/water (1:3))

ORD record

ord-2edddff5818d4378b1601cbf3a809109

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179912B2