Synthesis
A solution was prepared from diethyl 2-[(4-methoxyanilino)methylene]malonate (CAS: 83507-70-4, 71.4 g, 0.24 mol) in 150 mL of diphenyl ether. The reaction system was placed in a metal bath and slowly heated to 243 °C and maintained at this temperature for 3 hours. During the reaction, 15 mL of liquid was distilled. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently dissolved by adding 250 mL of hexane. After stirring the mixture for 3 hours, a filtration operation was performed. The resulting solid was washed with hexane and dried to give ethyl 4-hydroxy-6-methoxyquinoline-3-carboxylate (25.0 g, 0.10 mol, 41% yield), the purity of which meets the requirements for direct use in subsequent reactions. The structure of the product was confirmed by 1H-NMR (CDCl3) and LC-MS: 1H-NMR (CDCl3) δ= 1.28 (t, 3H), 3.85 (s, 3H), 4.21 (q, 2H), 7.34 (dd, 1H), 7.55-7.62 (m, 2H), 8.49 (s, 1H); LC-MS: Rt = 1.17 min ; MS: m/z = 248 [M + 1]+.
References
[1] Patent: WO2006/2047, 2006, A2. Location in patent: Page/Page column 60
[2] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 1 - 16
[3] Organic Process Research and Development, 2014, vol. 18, # 11, p. 1482 - 1491
[4] Tetrahedron Letters, 2017, vol. 58, # 8, p. 794 - 796
[5] Journal of the American Chemical Society, 1946, vol. 68, p. 1204,1206
