Synthesis
General procedure for the synthesis of 4-chloro-3-fluorophenylacetic acid from 3-fluoro-4-chlorophenylacetonitrile: A mixture of 3-fluoro-4-chlorophenylacetonitrile (7.8 g, 0.046 mol), water (7.5 mL), concentrated sulfuric acid (7.5 mL) and acetic acid (7.5 mL) was heated and refluxed for 2 hours. After the reaction was completed, the mixture was cooled to room temperature and then slowly poured into ice water. The precipitated solid product was collected by filtration and washed with ether to yield 4-chloro-3-fluorophenylacetic acid (6.8 g, 79% yield). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 3.64 (s, 2H), 7.14 (ddd, J = 0.6, 2.1, 8.2 Hz, 1H), 7.34 (dd, J = 2.1, 10.6 Hz, 1H), 7.52 (t, J = 8.1 Hz, 1H). Mass spectrum (ESI-) m/z: 187 [M-H]-.
References
[1] Patent: WO2010/31, 2010, A1. Location in patent: Page/Page column 55
[2] Patent: WO2010/32, 2010, A1. Location in patent: Page/Page column 54
[3] Patent: WO2010/30, 2010, A1. Location in patent: Page/Page column 48
