Synthesis
2-Fluoro-4-methylbenzonitrile (10 g, 74.07 mmol) was used as a raw material, which was dissolved in 200 mL of chloroform, 1 g of benzoyl peroxide (BPO) was added, and stirred until completely dissolved. Subsequently, N-bromosuccinimide (NBS, 19.77 g, 11.11 mmol) was added in batches and the reaction mixture was refluxed for 12 hours. After completion of the reaction, it was cooled to room temperature and washed three times with saturated aqueous sodium bicarbonate solution, then three times with appropriate amount of water and finally three times with saturated brine. The solvent was removed by evaporation under reduced pressure and purified by column chromatography to give the light yellow liquid product 4-cyano-3-fluorobenzyl bromide (14.00 g) in 88.79% yield.
References
[1] Patent: CN106810552, 2017, A. Location in patent: Paragraph 0068; 0070; 0071
[2] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 1325 - 1344
[3] Organic and Biomolecular Chemistry, 2004, vol. 2, # 9, p. 1339 - 1352
[4] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2925 - 2930
[5] Journal of the American Chemical Society, 2001, vol. 123, # 9, p. 2107 - 2108
