Synthesis
(4a) 4-Hydroxy-2-methylquinoline (17.4 g, 109 mmol) and phosphorus oxyfluoride (47.1 g, 164 mmol) were added in a round bottom flask. The reaction mixture was heated to 130 °C and maintained for several hours. After completion of the reaction, it was cooled to room temperature and the residue was partitioned between saturated Na2CO3 solution and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (5 × 300 mL). The organic layers were combined, washed sequentially with H2O (2 × 400 mL) and brine (1 × 400 mL), and dried with anhydrous MgSO4. After filtration, the filtrate was concentrated and the residue was purified by silica gel column chromatography to afford 4-bromo-2-methylquinoline (8.8 g, 36% yield).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 7, p. 1865 - 1870
[2] Patent: US2003/229084, 2003, A1. Location in patent: Page/Page column 33
[3] Patent: WO2017/36404, 2017, A1. Location in patent: Page/Page column 130
[4] Patent: EP96214, 1991, B1
[5] European Journal of Medicinal Chemistry, 2013, vol. 69, p. 527 - 536
