Synthesis
Example 59 Preparation of 2-fluoro-4-methylbenzonitrile: 3-fluoro-4-bromotoluene (70 g, 370 mmol) and cuprous cyanide (50 g, 555 mmol) were dissolved in N,N-dimethylformamide (300 mL), heated to reflux and maintained for 24 hours. Upon completion of the reaction, the mixture was cooled to room temperature, followed by the addition of concentrated ammonia (300 mL) and ether (200 mL) with continuous stirring for 1 hour. The reaction mixture was extracted with ether (3 x 200 mL). All organic phases were combined and washed sequentially with saturated saline (3 x 200 mL) and dried over anhydrous sodium sulfate. Finally, the solvent was removed by distillation under reduced pressure to afford the light yellow solid product 2-fluoro-4-methylbenzonitrile (44 g, 88% yield). Mass spectrometry analysis showed a molecular ion peak (M + H)+ of 136.
References
[1] Organic and Biomolecular Chemistry, 2004, vol. 2, # 9, p. 1339 - 1352
[2] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 20, p. 2925 - 2930
[3] Patent: WO2007/76092, 2007, A2. Location in patent: Page/Page column 74
[4] Journal of Organic Chemistry USSR (English Translation), 1992, vol. 28, # 7, p. 1135 - 1139
[5] Zhurnal Organicheskoi Khimii, 1992, vol. 28, # 7, p. 1439 - 1444
