Synthesis
General procedure for the synthesis of 2-(bromomethyl)-5-chlorobenzonitrile from 5-chloro-2-methylbenzonitrile: 5-chloro-2-methylbenzonitrile (3.02 g, 20 mmol) was dissolved in 70 mL of carbon tetrachloride. N-bromosuccinimide (NBS) (3.916 g, 22 mmol) and benzoyl peroxide (BPO) (0.194 g) were added to the solution, followed by heating and refluxing the mixture for 4 hours. After completion of the reaction, the reaction mixture was filtered while hot. The filtrate was concentrated to dryness by rotary evaporation and the resulting residue was dissolved in 20 mL of chloroform. The chloroform solution was washed sequentially with saturated sodium carbonate solution and water, followed by drying with anhydrous sodium sulfate (Na2SO4). The dried solution was again concentrated to dryness by rotary evaporation and finally purified by column chromatography (using petroleum ether as eluent) to give 3.532 g of white solid product in 77.1% yield.
References
[1] Patent: US2012/289497, 2012, A1. Location in patent: Page/Page column 27-28
[2] Patent: EP2524917, 2012, A1. Location in patent: Page/Page column 30-31
[3] Patent: EP2570125, 2013, A1. Location in patent: Paragraph 0136; 0137
[4] Patent: WO2013/37960, 2013, A1. Location in patent: Page/Page column 71
[5] Arzneimittel-Forschung/Drug Research, 1973, vol. 23, # 8, p. 1090 - 1100
