Synthesis
To synthesize 3-bromo-7-methoxyquinoline, 1.80 g (12.3 mmol, 1.1 eq.) of 2-bromomalonaldehyde was first dissolved in 30 mL of ethanol, followed by the addition of 1.25 mL of m-aminoanisole. The reaction mixture was stirred overnight at room temperature, then 20 mL of acetic acid was added and stirring was continued at 100 °C for 10 days. Upon completion of the reaction, the solvent was removed under vacuum using a rotary evaporator. The residual solid was partitioned between water and ethyl acetate. The aqueous phase was adjusted to alkaline with aqueous ammonia solution and the insoluble solid was filtered out. The filtrate was extracted with ethyl acetate, the organic phases were combined and dried with anhydrous magnesium sulfate. After filtration, the organic solvent was removed by rotary evaporator under vacuum. The crude product was purified by column chromatography using hexane/ethyl acetate (8:2, v/v) as eluent, resulting in 700 mg of the target product in 20% yield. The product characterization data were as follows: molecular formula C10H8BrNO; molecular weight 237/239; 1H-NMR (CDCl3) δ 8.76 (d, J = 2.2 Hz, 1H), 8.15 (d, J = 2.2 Hz, 1H), 7.55 (d, J = 9.1 Hz, 1H), 7.32 (d, J = 2.5 Hz, 1H), 7.15 (dd , J = 2.5 Hz, J = 8.8 Hz, 1H), 3.88 (s, 3H, OMe); 13C-NMR (CDCl3) δ 159.9, 150.4, 147.1, 135.9, 126.9, 123.4, 119.9, 113.6, 106.3, 54.6; IR (cm-1 ): 2961, 1620, 1581, 1491, 1462 1581, 1491, 1462, 1417, 1261, 1027, 796; MS (ESI): m/z 238-240 (M + H)+.
References
[1] Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2158 - 2169
[2] Patent: US2010/204234, 2010, A1. Location in patent: Page/Page column 12
[3] Patent: WO2012/83165, 2012, A1. Location in patent: Page/Page column 98
