Synthesis
4.2 Synthesis of 5-methoxyquinoline
(1) 5-Hydroxyquinoline (4.0 g, 27.6 mmol) was dissolved in anhydrous DMF (60 mL) under argon protection and cooled to 0 °C. NaH (1.33 g, 33.12 mmol, 60% mineral oil dispersion) was then slowly added. The reaction mixture was kept stirred at 0 °C for 30 min. Then, methyl iodide (4.7 g, 33.12 mmol) was added dropwise to the suspension and the reaction mixture was allowed to gradually warm up to room temperature with continued stirring for 30 min. Upon completion of the reaction, the reaction was quenched with 300 mL of water and then extracted with ether (6 x 100 mL). The organic layers were combined, washed sequentially with water and brine, dried with anhydrous Na2SO4, filtered and the solvent was concentrated under reduced pressure to give the brown oily target product 5-methoxyquinoline. Yield: 4.03 g (92%).
1H NMR (400 MHz, CDCl3) δ 8.95 (dd, J = 4.2, 2.0 Hz, 1H), 8.62 (dd, J = 8.4, 1.2 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.4 Hz, 1H), 7.42 (dd, J = 8.4, 4.4 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 4.05 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 155.17, 150.66, 148.70, 130.81, 129.37, 121.58, 120.85, 120.19, 104.22, 55.76.
References
[1] European Journal of Medicinal Chemistry, 2015, vol. 101, p. 754 - 768
[2] Patent: KR101778938, 2017, B1. Location in patent: Paragraph 0147-0148; 0155; 0164-0166
[3] Dissertation , S. 23,
[4] Chemische Berichte, 1882, vol. 15, p. 1979
[5] Chemische Berichte, 1887, vol. 20, p. 731
