Step G (2): synthesis of 3-bromo-5-(methoxycarbonyl)benzoic acid. To a mixed solution containing copper(II) bromide (5.5 g, 24.6 mmol), tert-butyl nitrite (3.17 g, 30.75 mmol), and acetonitrile (300 mL) was slowly added a solution of acetonitrile (300 mL) of 3-amino-5-(methoxycarbonyl)benzoic acid (4.0 g, 20.5 mmol) for 30 min at 0 °C. Subsequently, the reaction mixture was warmed to room temperature and stirring was continued for 3 hours. Upon completion of the reaction, water was added and the acetonitrile was removed by distillation under reduced pressure. To the residue, ethyl acetate (600 mL) was added, and the organic layer was washed sequentially with 3N HCl, water, dried with anhydrous Na2SO4, and concentrated under reduced pressure to afford the target product methyl 3-bromo-5-carboxybenzoate in 97% yield. The product was characterized as follows: 1H NMR (CDCl3, 500 MHz) δ 3.96 (3H, s), 8.41 (1H, s), 8.67 (1H, s); MS (ESI) m/z 259.02 (M-H)-.
