Synthesis
Step 5) Synthesis of 4-(2-fluoro-4-nitrophenoxy)quinolin-7-ol: 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)quinoline (100 g, 256.4 mmol) was suspended in dioxane (425 mL) and concentrated hydrochloric acid (425 mL, 5.1 mol) was added. The reaction mixture was stirred at 100 °C for 24 hours. Upon completion of the reaction, the mixture was cooled to room temperature and the precipitated solid was collected by filtration. The resulting solid was suspended in anhydrous ethanol (100 mL), stirred and the solid was collected by filtration again. Finally, the solid was dried under vacuum at 60 °C for 12 h to give the title compound as a light-colored solid (73.3 g, 85% yield). m/z MS (ESI, cationic): 301 [M +1]+; 1H NMR (400 MHz, DMSO-d6): δ 7.06-7.07 (d, J = 6.8 Hz, 1H), 7.51-7.54 (m 1H), 7.71 (s, 1H), 7.89-7.94 (m, 1H), 8.28-8.30 (d, J = 8.8 Hz, 1H), 8.41-8.43 (d, J = 9.6 Hz, 1H), 8.51-8.54 (d, J = 10 Hz, 1H), 8.94-8.96 (d, J = 6.4 Hz, 1H), and 12.00 (s, 1H).
References
[1] Patent: US2012/219522, 2012, A1. Location in patent: Page/Page column 20
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 6277 - 6292
