Synthesis
General procedure for the synthesis of ethyl 4-hydroxyquinoline-3-carboxylate from diethyl 2-phenylaminomethylidene-malonate: In a 1L three-necked flask fitted with a mechanical stirrer, diethyl 2-phenylaminomethylidene-malonate (26.3 g, 0.100 mol), polyphosphoric acid (270 g), and phosphorochloride (750 g) were added. The reaction mixture was heated to 70 °C and stirred at this temperature for 4 hours. After completion of the reaction, the mixture was cooled to room temperature and then filtered. The filtered residue was treated with aqueous sodium carbonate (Na2CO3), filtered again, washed with water and finally dried. Ethyl 4-hydroxyquinoline-3-carboxylate was obtained as a light brown solid (15.2 g, 70% yield).
References
[1] Patent: US4079058, 1978, A
[2] Patent: US2008/90864, 2008, A1. Location in patent: Page/Page column 7
[3] Patent: WO2007/79139, 2007, A2. Location in patent: Page/Page column 46
[4] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[5] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2000, vol. 344, p. 163 - 168
