Synthesis
The general procedure for the synthesis of 2-(4-fluorophenyl)propionic acid from the compound (CAS: 50415-71-9) was as follows: under stirring conditions, racemic methyl 2-(4-thieno-phenyl)propionate (18.9 g) was dissolved in ethanol (200 mL) and an aqueous solution of potassium hydroxide (35 g) (200 mL) was slowly added. The reaction mixture was stirred continuously at 0 °C for 4 hours. Upon completion of the reaction, the pH was adjusted to 5 with 4.0 M hydrochloric acid, followed by extraction of the reaction mixture with ethyl acetate. The organic phase was separated and the solvent was removed by distillation under reduced pressure to give 15.64 g of 2-(4-fluorophenyl)propionic acid as a crude product. The crude product could be used directly in the subsequent reaction without further purification. The structure of the product was confirmed by 1H-NMR (300 MHz, DMSO-d6): δ [ppm] = 1.31 (d, 3H), 3.66 (q, 1H), 7.05-7.15 (m, 2H), 7.24-7.33 (m, 2H), 12.30 (s, 1H).
References
[1] Organic letters, 2002, vol. 4, # 3, p. 371 - 373
[2] Journal of Organic Chemistry, 2003, vol. 68, # 19, p. 7234 - 7242
[3] Patent: WO2010/31183, 2010, A1. Location in patent: Page/Page column 18
[4] Patent: WO2013/87579, 2013, A1. Location in patent: Page/Page column 134; 135
[5] Patent: WO2014/9219, 2014, A1. Location in patent: Page/Page column 107; 108
