Uses
Methyl 2-fluoro-4-hydroxybenzoate can be used in the preparation of compounds, with the ability to inhibit cytosolic phospholipase A2α. It is also an intermediate in the synthesis of 3-(2-fluoro-4-hydroxyphenyl)-5-(trifluoromethyl) -4-isoxazolecarboxylic acid methyl ester (F591865).
Synthesis
General procedure for the synthesis of methyl 2-fluoro-4-hydroxybenzoate from methanol and 2-fluoro-4-hydroxybenzoic acid: Referring to Example 10 of the literature; 2-fluoro-4-hydroxybenzoic acid (50.0 g) was dissolved in methanol (700 mL), concentrated sulfuric acid (10 mL) was added as a catalyst, and the reaction was carried out with heating and stirring for 16 hrs. at 90 °C. After the reaction was completed, the reaction solution was concentrated, and the resulting colorless crystals were washed with water and dried to obtain the target product methyl 2-fluoro-4-hydroxybenzoate (51 g, 94% yield) as colorless crystals. The product was characterized by 1H NMR (300 MHz, DMSO-d6): δ 3.79 (3H, s), 6.61-6.72 (2H, m), 7.73-7.79 (1H, m), 10.80 (1H, br).
References
[1] Patent: EP2392573, 2011, A1. Location in patent: Page/Page column 39
[2] Patent: EP2522657, 2012, A1. Location in patent: Page/Page column 36-37
[3] Patent: WO2010/45258, 2010, A2. Location in patent: Page/Page column 140; 141
[4] Patent: WO2009/111056, 2009, A1. Location in patent: Page/Page column 212
[5] ChemMedChem, 2013, vol. 8, # 5, p. 779 - 799
