Hydrochloric Acid → 4-Iodo-7-methoxyquinoline

Participants

Reaction Steps

The general procedure is described in Drake, N. L.; Creech, H. J.; Garman, J. A.; Haywood, S. T.; Peck, R. M.; Van Hook, J. O.; Walton, E., Synthetic antimalarials. The preparation of certain 4-aminoquinolines. Journal of the American Chemical Society 1946, 68, 1208-13. A dry 250 mL, 1-neck round bottomed flask was charged with 4-chloro-7-methoxyquinoline (1.77 g, 9.1 mmol), and 100 mL dry dioxane. The solution was treated with 20 mL 1N HCl in Et2O. The solution was occasionally swirled over a 15 minute period, and the solvent was removed in vacuo. The residue was dried at 60° C. at 0.1 mmHg for 2 h. To the flask was added a stir bar and 20 mL dry acetonitrile. The flask was fitted with a reflux condenser, and to the stirring slurry was added sodium iodide (4.1 g, 27 mmol). The solution was heated to reflux for 48 h. The solution was cooled, and the solution was filtered. The precipitate was washed with ACN (3×20 mL), and water (3×20 mL). The solid was suspended in 70% CH2Cl2-30% MeOH. To the solution was added Si-carbonate (16 g, 11 mmol). The slurry was swirled for 1 h, and filtered. The silica was washed with EtOH (3×50 mL). The solvent was removed in vacuo to afford 4-iodo-7-methoxyquinoline. 1H NMR (300 MHz, MeOD) δ ppm 4.00 (s, 3 H) 7.35 (dd, J=10.01, 2.48 Hz, 1 H) 7.36 (d, J=2.56 Hz, 1 H) 8.00 (d, J=9.87 Hz, 1 H) 8.01 (d, J=4.75 Hz, 1 H) 8.33 (d, J=4.90 Hz, 1 H). 13C NMR (101 MHz, MeOD) δ ppm 56.46 (s, 1 C) 107.73 (s, 1 C) 113.18 (s, 1 C) 122.61 (s, 1 C) 127.31 (s, 1 C) 132.05 (s, 1 C) 134.27 (s, 1 C) 150.18 (s, 1 C) 150.86 (s, 1 C) 163.35 (s, 1 C). MS (ESI pos. ion) m/z (MH+): 286.0, calcd for C10H8INO+H+=286.0.

Provenance & Evidence