General procedure for the synthesis of 4-hydroxy-6-methoxyquinoline-3-carboxylic acid from ethyl 4-hydroxy-6-methoxyquinoline-3-carboxylate: ethyl 4-hydroxy-6-methoxyquinoline-3-carboxylate (17.8 g, 72 mmol) was suspended in 170 mL of aqueous 2 N sodium hydroxide solution, heated to 90 °C, and the reaction was maintained for 1.5 h. The mixture was cooled to room temperature and slowly poured into ice water. Upon completion of the reaction, the mixture was cooled to room temperature, slowly poured into ice water and the pH was adjusted to 5 with 2 N hydrochloric acid.The precipitated solid was collected by filtration, washed with cold water and dried to give 4-hydroxy-6-methoxyquinoline-3-carboxylic acid (15.8 g, 72 mmol, 99% yield). The product was characterized by 1H-NMR (DMSO-d6): δ= 3.91 (s, 3H), 7.53 (dd, 1H), 7.64 (d, 1H), 7.82 (d, 1H), 8.80 (d, 1H), 13.63 (bs, 1H), 15.55 (s, 1H).Results of LC-MS analysis: retention time (Rt) = 1.20 min; Mass spectrum (MS): m/z = 220 [M+H]+.
