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Step 5 Synthesis of 8-bromo-6-methoxyquinoline: To a solution of 5.05 g (29.0 mmol) of 6-methoxy-8-aminoquinoline in 25 mL of 48% hydrobromic acid (HBr) was added a 20 mL aqueous solution of 2.60 g (37.7 mmol) of sodium nitrite (NaNO2) at 0 °C. After stirring at 0°C for 15 minutes, the resulting mixture was added dropwise to a solution of 5.0 g (34.8 mmol) of cuprous bromide (CuBr) and 60 mL of 48% hydrobromic acid (HBr) preheated to 75°C. After 5.5 hours of reaction, the reaction mixture was neutralized with 150 mL of ice-cold 5N sodium hydroxide (NaOH) solution, followed by stirring the resulting mixture with 300 mL of ethyl acetate (EtOAc) and filtration through a diatomaceous earth pad. The filtrate was extracted with 2 x 100 mL of ethyl acetate (EtOAc), the organic phases were combined, washed sequentially with 1 x 200 mL of water (H2O), 1 x 200 mL of brine, dried with anhydrous sodium sulfate (Na2SO4), and the volatiles were evaporated after filtration. The resulting crude product was purified by column chromatography on silica gel (SiO2) with the eluent of petroleum ether/ethyl acetate (4/1 to 1/1) to afford 4.23 g (17.8 mmol, 61% yield) of the target compound 8-bromo-6-methoxyquinoline as a brown oil. Mass spectrum (ES) m/z 239 (MH)+.

[1] Patent: US2003/32645, 2003, A1
[2] Zhurnal Obshchei Khimii, 1941, vol. 11, p. 537,538
[3] Chem.Abstr., 1941, p. 6961
[4] Journal of the American Chemical Society, 1951, vol. 73, p. 4837