[Synthesis]
Step 1: Under nitrogen protection, 3-bromoquinoline (6.5 mL, 48 mmol) was dissolved in anhydrous dimethylformamide (80 mL), followed by the addition of 30% sodium methanol solution (16 mL, 54 mmol) and copper iodide (458 mg, 2.4 mmol). The reaction mixture was heated to reflux with continuous stirring for 16 hours. After completion of the reaction, the mixture was cooled to room temperature and hydrolyzed by adding water. The reaction mixture was extracted with ether (Et2O) and the organic layer was separated. The organic layer was washed sequentially with water and saturated brine and dried over anhydrous magnesium sulfate. After filtration, the organic phase was concentrated under reduced pressure to give 3-methoxyquinoline as a colorless oil in 94% yield. The product was confirmed by 1H NMR (300 MHz, CDCl3) and mass spectrometry (APCI, pos. 30V): 1H NMR δ 8.45 (d, 1H, J=2.9 Hz), 7.85 (dd, 1H, J=8.1, 1.2 Hz), 7.49 (dd, 1H, J=8.1, 1.2 Hz), 7.36-7.25 (m, 2H) , 7.12 (d, 1H, J=2.9 Hz), 3.67 (s, 3H); MS m/z: [M+H]+ 160. |
[References]
[1] European Journal of Medicinal Chemistry, 2017, vol. 127, p. 621 - 631
[2] Tetrahedron, 2002, vol. 58, # 6, p. 1125 - 1129 |