Example 8: Synthesis of Compound XIII-6; Step 1: Synthesis of 2-(bromomethyl)-1-methoxy-4-nitrobenzene (2); A mixture of 4-nitroanisole (1,1 g, 6.529 mmol), paraformaldehyde (0.218 g) and sodium bromide (0.8 g) in glacial acetic acid (1.3 mL) was heated to 85 °C. Sulfuric acid (0.8 mL) and glacial acetic acid (0.8 mL) were slowly added dropwise to the reaction mixture over a period of 5 hours. The reaction mixture was continued to be stirred at 85°C for 3 hours, followed by stirring at 28°C for 12 hours. After completion of the reaction, the reaction mixture was extracted with ether, the ether layer was washed sequentially with 5% sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford 2-(bromomethyl)-1-methoxy-4-nitrobenzene (2,0.965 g, 60% yield).NMR (400 MHz, CDCl3): δ 8.30-8.22 (m, 2H), 7.00-6.95 (d, 1H), 4.55 (s, 2H), 4.05 (s, 3H).
