Synthesis
General procedure for the synthesis of 4-cyano-2-fluorobenzyl bromide from 3-fluoro-4-methylbenzonitrile: 3-fluoro-4-methylbenzonitrile (40 g, 296 mmol), N-bromosuccinimide (NBS, 63.2 g, 356 mmol), and benzoyl peroxide (3.6 g, 14.8 mmol) were dissolved in carbon tetrachloride (490 mL), and the reaction was performed at reflux for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered. The filtrate was concentrated and purified by fast column chromatography (eluent: 0-5% ethyl acetate/hexane) to afford the target product 4-(bromomethyl)-3-fluorobenzonitrile (35.4 g, 56% yield).
References
[1] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 12, p. 1647 - 1650
[2] Organic and Biomolecular Chemistry, 2004, vol. 2, # 9, p. 1339 - 1352
[3] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 12, p. 1203 - 1207
[4] Patent: WO2016/109361, 2016, A2. Location in patent: Paragraph 00144
[5] Patent: US2010/240719, 2010, A1. Location in patent: Page/Page column 11
