Synthesis
General procedure for the synthesis of 4-hydroxy-7-methoxyquinoline-3-carboxylic acid from ethyl 4-hydroxy-7-methoxyquinoline-3-carboxylate: ethyl 4-hydroxy-7-methoxyquinoline-3-carboxylate (4.40 g, 17.80 mmol) was dissolved in 2 M NaOH solution and hydrolyzed by refluxing the reaction for 1 h at 110 °C. The mixture was cooled to room temperature and acidified with 2 M HCl solution. After completion of the reaction, the mixture was cooled to room temperature and acidified to pH 3-4 with 2 M HCl solution.After acidification, the precipitated white precipitate was collected by filtration, washed with water and dried to afford the target product 4-hydroxy-7-methoxyquinoline-3-carboxylic acid (2.50 g, 63% yield) with a melting point of 272 °C (literature value: Lauer et al., 1946, 257-260 °C). NMR hydrogen spectrum (400 MHz, DMSO-d6) δ: 3.90 (3H, s, OCH3), 7.17 (1H, dd, J = 2.4, 9.0 Hz, H-6), 7.29 (1H, d, J = 2.3 Hz, H-8), 8.16 (1H, d, J = 9.0 Hz, H-5), 8.72 (1H, s, H-2). 13.68 (1H, s, Ar-OH), 15.50 (1H, bs, -COOH). NMR carbon spectrum (100 MHz, DMSO-d6) δ: 56.3 (Ar-OCH3), 101.1 (C-3), 107.8 (C-8), 116.6 (C-4a), 118.9 (C-6), 127.3 (C-5), 142.0 (C-2), 145.0 (C-8a), 163.8 (C-4). 166.9 (C-7), 178.1 (COOH).
References
[1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 13, p. 3738 - 3748
[2] Journal of the American Chemical Society, 1946, vol. 68, p. 1268
[3] Journal of Medicinal Chemistry, 1998, vol. 41, # 25, p. 4918 - 4926
[4] Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 5, p. 821 - 824
[5] Patent: US6110929, 2000, A
