General procedure for the synthesis of 6-bromo-7-fluoroquinoline from 4-bromo-3-fluoroaniline and glycerol:
Intermediate 2: (7-fluoroquinolin-6-yl)methylamine
Step 1: Synthesis of 6-bromo-7-fluoroquinoline: 4-bromo-2-fluoroaniline (10 g, 52.62 mmol), ferrous sulfate (3.33 g, 11.97 mmol) and glycerol (15.78 mL) were mixed. Concentrated sulfuric acid (9.15 mL) was added slowly and the reaction mixture was heated to 140 °C. After 12 hours of reaction, the mixture was cooled to 0 °C and the pH was adjusted to 10-12 with 10% sodium hydroxide solution.The reaction mixture was filtered through diatomaceous earth and washed with ethyl acetate to separate the organic and aqueous layers. The organic layer was washed with brine solution, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by column chromatography (eluent: ethyl acetate/petroleum ether) to give the title compound as a white solid (4.9 g, 44% yield).
1H-NMR (δppm, CDCl3, 400MHz): δ 8.96 (dd, J=4.3,2.7Hz, 1H), 8.15 (m, 2H), 7.81 (d, J=9.5Hz, 1H), 7.42 (dd, J=8.3,4.3Hz, 1H).
