Synthesis
To a methanol (MeOH) solution of 2-methylbenzaldehyde (10.0 g, 83.23 mmol) was slowly added aqueous methylamine (40%, 25.85 g, 332.9 mmol) at 25 °C. The reaction mixture was stirred continuously at 25 °C for 30 min and subsequently cooled to 0 °C. At this temperature, sodium borohydride (NaBH4, 6.30 g, 166.5 mmol) was added in batches. After addition, the reaction mixture was slowly warmed to 25 °C and stirring was continued for 1 hour. After completion of the reaction, the solvent was removed by distillation under reduced pressure. Water and dichloromethane (CH2Cl2) were added to the residue and the organic layer was separated. The organic layer was washed sequentially with saturated sodium bicarbonate (NaHCO3) solution and brine and dried over anhydrous sodium sulfate (Na2SO4). The organic phase was concentrated under reduced pressure to afford the target product N,2-dimethylbenzylamine (10.49 g, 93.2% yield) as an oil of sufficient purity for direct use in subsequent reactions. The product was detected by mass spectrometry (APCI+) showing m/z 136.3 ([M+H]+), and the nuclear magnetic resonance hydrogen spectroscopy (1H-NMR, CDCl3) data were as follows: δ 7.35-7.08 (m, 3H), 3.73 (s, 2H), 2.49 (s, 3H), 2.34 (s, 3H).
References
[1] Patent: US2006/111422, 2006, A1. Location in patent: Page/Page column 53
[2] Journal of the American Chemical Society, 1940, vol. 62, p. 910
[3] Patent: US2006/52378, 2006, A1. Location in patent: Page/Page column 111
[4] European Journal of Medicinal Chemistry, 2018, vol. 143, p. 390 - 401
