METHYL 2-FLUORO-6-HYDROXYBENZOATE

67-56-1

67531-86-6

72373-81-0

Procedure for the synthesis of methyl 2-fluoro-6-hydroxybenzoate (2): 2-fluoro-6-hydroxybenzoic acid (Oakwood Products; 0.972 kg, 6.31 mol), methanol (7.60 L), and sulfuric acid (0.710 kg, 7.24 mol, 1.15 eq.) were added to a 20 L jacketed reactor. The jacket temperature was raised to 60°C and the reaction mixture was stirred continuously for 45 hours. Upon completion of the reaction, about 7.5 L of methanol distillate was removed by vacuum concentration. The residue was cooled to 20 °C and extracted by adding water (7.60 L) and ethyl acetate (7.60 L) to transfer the product to the organic layer. The ethyl acetate layer was washed sequentially with aqueous sodium bicarbonate (1.52 Kg sodium bicarbonate dissolved in 6.92 L water) and aqueous sodium chloride (1.74 kg sodium chloride dissolved in 4.08 L water). The washed ethyl acetate solution was concentrated to dryness to give a light orange colored oily substance. After standing, the oily material gradually crystallized to give the target product methyl 2-fluoro-6-hydroxybenzoate (2) (0.952 Kg, 5.60 mol, 89% yield). The product was analyzed by 1H NMR, 13C NMR and mass spectrometry to confirm the structure.