Synthesis
1. 4-Cyanobenzyl bromide (2.28 g, 11.6 mmol) was dissolved in 25 mL of anhydrous acetonitrile under nitrogen protection.
2. To the above solution, morpholine (1.5 mL, 17.4 mmol) and potassium carbonate (0.69 g, 5 mmol) were added sequentially.
3. Stir the reaction mixture for 30 minutes at room temperature. 4.
4. Upon completion of the reaction, the reaction was quenched with water and extracted with ethyl acetate.
5. The organic layers were combined, dried over anhydrous magnesium sulfate and subsequently concentrated under reduced pressure. 6.
6. The crude product was purified by column chromatography (eluent: hexane-30% ethyl acetate/hexane) to give 4-(4-morpholinylmethyl)benzonitrile. 7. The product was a white solid.
7. The product was a white solid in 96% yield. 8.
8. 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 7.9 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 3.71 (s, 4H), 3.55 (s, 2H), 2.44 (s, 4H); 13C NMR (100 MHz, CDCl3): 144.2, 132.5, 129.8, 119.2, 129.8, 119.2 129.8, 119.2, 111.3, 67.2, 63.1, 54.1.
References
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 5, p. 1844 - 1857
[2] Patent: WO2012/69856, 2012, A1. Location in patent: Page/Page column 67
[3] European Journal of Medicinal Chemistry, 2018, vol. 152, p. 31 - 52
[4] Patent: WO2013/153357, 2013, A1. Location in patent: Page/Page column 20; 41; 42
[5] Patent: US2015/45354, 2015, A1. Location in patent: Paragraph 0251-0254
