Synthesis
GENERAL STEPS: Methylamine (350 mL, 40% aqueous, 4.06 mol) was slowly added to a solution of 4-(bromomethyl)benzonitrile (51.3 g, 262 mmol) in ethanol (500 mL) and the reaction was stirred at room temperature for 2 hours. Upon completion of the reaction, the solvent was removed by rotary evaporator under reduced pressure. To the residue, dichloromethane (500 mL) and saturated aqueous sodium bicarbonate (400 mL) were added, mixed thoroughly and left to partition. The organic phase was separated and washed with saturated aqueous sodium chloride solution (250 mL) and subsequently dried over anhydrous sodium sulfate. After filtering to remove the desiccant, the organic phase was concentrated under reduced pressure. The resulting residue was dissolved in a solution of 1 M hydrochloric acid in ether (300 mL), stirred for 30 minutes, filtered and the solid was washed with ether. The solid was dissolved in water (500 mL) and the pH was adjusted to alkaline with 6 M aqueous sodium hydroxide, followed by extraction with dichloromethane (500 mL). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and the solvent was concentrated under reduced pressure to afford the target product N-methyl-4-cyanobenzylamine. Yield: 31.17 g, 81% yield.
References
[1] Patent: US2008/153843, 2008, A1. Location in patent: Page/Page column 88
[2] Patent: WO2012/101453, 2012, A1. Location in patent: Page/Page column 41
[3] Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 309 - 312
[4] Journal of Medicinal Chemistry, 1986, vol. 29, # 1, p. 40 - 44
[5] Journal of Medicinal Chemistry, 1998, vol. 41, # 15, p. 2882 - 2891
