Synthesis
Ethyl 6-bromo-4-hydroxyquinoline-3-carboxylate (11 g, 37 mmol) was suspended in anhydrous dimethylformamide (148.6 mL) under nitrogen protection. Phosphoryl chloride (20.7 mL, 222 mmol, 6 equiv) was added slowly using a syringe. After addition, the reaction mixture was stirred vigorously for 3 hours at room temperature. Upon completion of the reaction, the mixture was slowly poured into ice water (1.5 L) and stirred continuously until the ice was completely melted. The precipitated solid product was collected by filtration, washed well with water until the washings were neutral, and subsequently dried under vacuum to constant weight. Ethyl 4-chloro-6-bromoquinoline-3-carboxylate (11.4 g, 94% yield) was finally obtained. Mass spectra (ESI) m/z (M + H) + 314.0, 316.0.
References
[1] Patent: US2012/184577, 2012, A1. Location in patent: Page/Page column 2; 3
[2] Patent: CN105859684, 2016, A. Location in patent: Paragraph 0148; 0149; 0150
[3] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 24, p. 7585 - 7596
[4] RSC Advances, 2017, vol. 7, # 4, p. 2342 - 2350
[5] European Journal of Medicinal Chemistry, 2017, vol. 127, p. 509 - 520
