Synthesis
GENERAL METHOD: Diethyl [[[(trifluoromethyl)phenyl]amino}methylene]malonate (10.0 g, 0.030 mol) was mixed with Dowtherm (100 mL), heated to 250 °C and maintained at this temperature for 5 hours of reaction. Upon completion of the reaction, the mixture was cooled to 25 °C, followed by the addition of 150 mL of hexane and stirred for 10 minutes. The resulting solid product was collected by filtration and dried. The crude product was further purified by column chromatography with the eluent being a solvent mixture of petroleum ether and ethyl acetate (5:5, v/v), resulting in ethyl 4-hydroxy-8-trifluoromethylquinoline-3-carboxylate in white solid form.
References
[1] European Journal of Medicinal Chemistry, 2013, vol. 68, p. 422 - 432
[2] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 324 - 332
[3] Patent: US2005/131014, 2005, A1. Location in patent: Page/Page column 28
[4] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 3, p. 1040 - 1044
[5] Organic Process Research and Development, 2014, vol. 18, # 11, p. 1482 - 1491
