Uses
Methyl 4-amino-3-hydroxybenzoate is used as an important raw material and intermediate used in Organic Synthesis, Pharmaceuticals, Agrochemicals and Dyestuff.
Synthesis
1. 4-Amino-3-hydroxybenzoic acid (5.0 g, 32.6 mmol) was slowly added dropwise to a mixture of 1.25 M HCl solution (100 mL) and methanol (100 mL) at 0 °C.
2. After the dropwise addition, the reaction mixture was gradually warmed up to room temperature with continuous stirring overnight.
3. The reaction process was monitored by HPLC and it was found that there was still raw material left, so the mixture was continued to be stirred at room temperature for 48 hours.
4. After completion of the reaction, the solvent was removed by distillation under reduced pressure. 5.
5. The residue was treated with saturated aqueous sodium bicarbonate solution, followed by extraction of the aqueous phase with ethyl acetate (2×).
6. The organic extracts were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to dryness to afford the title compound methyl 4-amino-3-hydroxybenzoate (5.37 g, 97% yield) as a crystalline solid.
7. The molecular weight of the product was confirmed to be 168 (M+1)+ by low resolution mass spectrometry (LRMS) analysis.
References
[1] Patent: WO2013/68552, 2013, A1. Location in patent: Page/Page column 70
[2] Patent: WO2013/68554, 2013, A1. Location in patent: Page/Page column 80
[3] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 10, p. 1257 - 1260
[4] Patent: EP1382607, 2004, A2. Location in patent: Page 43
[5] Organic and Biomolecular Chemistry, 2016, vol. 14, # 15, p. 3782 - 3786
