Synthesis
General procedure for the synthesis of 3-fluoro-4-hydroxyphenylacetic acid from 3-fluoro-4-methoxyphenylacetic acid: Aluminum chloride (42.8 g, 0.32 mol) was slowly added to 500 mL of toluene solution containing 3-fluoro-4-methoxyphenylacetic acid (45 g, 0.245 mol), and the temperature of the reaction was controlled to be no more than 25 °C. Subsequently, the reaction mixture was heated to reflux for 5 hours. Upon completion of the reaction, 260 mL of 10% hydrochloric acid was added to the cooled solution. The precipitate was collected by filtration and the filtrate was extracted twice with 75 mL of 1,2-dichloroethane. The organic extracts were combined and washed sequentially with 5% sodium hydroxide solution and water. The alkaline washings were combined with the previously collected precipitate and filtered through activated carbon after adjusting the pH to 12 with 5% sodium hydroxide solution. The filtrate was acidified with 50% sulfuric acid and the resulting oil was extracted with ether. The organic phase was dried and the solvent was evaporated to give 3-fluoro-4-hydroxyphenylacetic acid in a yield of 25 g (62% yield). The melting point of the product was 109-111 °C. Mass spectrum (ESI) m/z (relative abundance): 193.0 [M + Na]+.
References
[1] Collection of Czechoslovak Chemical Communications, 1990, vol. 55, # 1, p. 296 - 306
[2] European Journal of Medicinal Chemistry, 2014, vol. 87, p. 508 - 518
[3] Chemische Berichte, 1952, vol. 85, p. 577,580
[4] DRP/DRBP Org.Chem.,
