Synthesis
The general synthetic route of the compound is schematically described in Scheme 1.The synthesis of 2,4-dichloro-8-methoxyquinoline was carried out with reference to literature reports [27,28] as follows: equimolar o-methoxyaniline and malonic acid were mixed with 30 mL of phosphorochloridic acid and refluxed for 5 h on a heating mantle kept at 80-100°C. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was cooled to room temperature and slowly poured into crushed ice with continuous stirring. The precipitated solid was separated by filtration, dried and washed thoroughly with water. The crude product was purified by column chromatography (eluent ratio 95:5 hexane-ethyl acetate) to afford 2,4-dichloro-8-methoxyquinoline in 78.6% yield.
References
[1] Journal of Molecular Structure, 2017, vol. 1131, p. 51 - 72
[2] Research on Chemical Intermediates, 2014, vol. 40, # 5, p. 1851 - 1866
[3] Medicinal Chemistry, 2015, vol. 11, # 8, p. 789 - 797
[4] Organic Process Research and Development, 2016, vol. 20, # 2, p. 215 - 226
[5] Journal of Organic Chemistry, 2013, vol. 78, # 21, p. 10605 - 10616
