[Synthesis]
Diethyl 2-(2-bromo-4-fluorobenzyl)-malonate (2.1 g, 6.07 mmol) was used as a raw material, which was mixed with water (14 mL) and potassium hydroxide (0.68 g, 12.14 mmol) was added. The reaction mixture was heated under reflux conditions for 4.5 hours. Upon completion of the reaction, the mixture was cooled to room temperature and ethanol was removed by distillation under reduced pressure. The aqueous residue was cooled to 100°C, acidified with concentrated sulfuric acid and subsequently heated at 120°C for 16 hours. After the reaction mixture was cooled to 0°C, the precipitated solid was collected by filtration, washed with water and dried to afford 3-(2-bromo-4-fluorophenyl)propionic acid as an off-white solid (0.5 g, 33% yield). Thin layer chromatography (TLC) showed an Rf value of 0.2 (unfolding agent: 30% ethyl acetate/petroleum ether).1H NMR (400 MHz, DMSO-d6) data were as follows: δ 12.26 (s, 1H), 7.55-7.52 (m, 1H), 7.42-7.38 (m, 1H), 7.23-7.18 (m, 1H), 2.90 (t. J = 7.8 Hz, 2H), 2.52 (t, J = 7.8 Hz, 2H). |