6-Bromo-4-chloro-3-nitroquinoline

Synthesis

Step 3: 6-bromo-4-hydroxy-3-nitroquinoline (product of Step 2, 20 g, 74.3 mmol) was mixed with phosphorus oxychloride (POCl3, 150 mL, 1613 mmol) and the reaction was stirred for 45 minutes. Upon completion of the reaction, the mixture was cooled to room temperature and slowly poured into ice water to quench the reaction. The precipitated solid was collected by filtration, washed with ice-cold water and subsequently dissolved in dichloromethane (CH2Cl2). The organic layer was washed with cold saturated saline and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed by evaporation under reduced pressure to give 6-bromo-4-chloro-3-nitroquinoline. Yield: 8 g (38%); 1H NMR (CDCl3, 500 MHz): δ 9.275 (s, 1H), 8.611-8.615 (d, 1H, J = 2 Hz), 8.100-8.118 (d, 1H, J = 9 Hz), 8.026-8.048 (dd, 1H, J = 8.5 Hz, 2 Hz).

References

[1] Patent: US2015/320727, 2015, A1. Location in patent: Paragraph 0555; 0556
[2] Patent: WO2015/145369, 2015, A1. Location in patent: Page/Page column 38
[3] Patent: WO2009/155527, 2009, A2. Location in patent: Page/Page column 142
[4] MedChemComm, 2016, vol. 7, # 2, p. 297 - 310
[5] Patent: CN108456165, 2018, A. Location in patent: Paragraph 0047; 0081-0082