Synthesis
The general procedure for the synthesis of 2-(bromomethyl)-5-fluorobenzonitrile from 5-fluoro-2-methylbenzonitrile was as follows: first, 5-fluoro-2-methylbenzonitrile (28.51 g, 211 mmol), N-bromosuccinimide (NBS, 41.31 g, 232 mmol), and azobisisobutyronitrile (AIBN, 2.5 g, 15 mmol) were added to a carbon tetrachloride ( CCl4, 845 mL) in a mixture of nitrogen (N2) was passed for 10 min. Subsequently, the reaction mixture was heated to reflux for 8 hours. After completion of the reaction, the mixture was allowed to stand at room temperature overnight. On the following day, the reaction mixture was filtered and the filter cake was washed with carbon tetrachloride (500 mL). The filtrates were combined and the solvent was removed by evaporation to give a yellow oil. Finally, 2-(bromomethyl)-5-fluorobenzonitrile (29.74 g, 66% yield) was obtained as a light yellow oil using 5-25% ethyl acetate/hexane as eluent and purified by fast column chromatography on silica gel (SiO2). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3) with chemical shift δ: 7.55 (1H, dd, J = 8.6,5.2 Hz), 7.37 (1H, dd, J = 7.9,2.8 Hz), 7.32-7.28 (1H, m), 4.61 (2H, s).
References
[1] Patent: US2005/267105, 2005, A1. Location in patent: Page/Page column 63
[2] Patent: US2007/111984, 2007, A1. Location in patent: Page/Page column 29
[3] Patent: US2007/129379, 2007, A1. Location in patent: Page/Page column 22
[4] Patent: WO2007/64316, 2007, A1. Location in patent: Page/Page column 141
[5] Organic and Biomolecular Chemistry, 2013, vol. 11, # 19, p. 3128 - 3144
