Under argon protection, dimethyl 5-aminoisophthalate (1) (6.27 g, 30.0 mmol) was added to 39 mL of 2 M hydrochloric acid pre-cooled in an ice bath. The reaction mixture was stirred at 0 °C or lower for several minutes before 21.6 mL of pre-cooled aqueous sodium nitrite (2.52 g, 36.5 mmol, 1.2 eq.) was added slowly and dropwise. Subsequently, 30 mL of dichloromethane was added and stirring was continued for 5 hours after the reaction mixture was brought to room temperature. Upon completion of the reaction, 70 mL of aqueous potassium iodide (7.47 g, 45.0 mmol, 1.5 eq.) was added slowly and dropwise under ice bath cooling conditions and the mixture was stirred at room temperature for 12 hours. At the end of the reaction, the aqueous layer was extracted with ethyl acetate, the organic layer was washed with saturated brine, dried with anhydrous magnesium sulfate, and purified by silica gel column chromatography (silica gel, hexanes as eluent) to afford the target product dimethyl 5-iodoisophthalate (2) (5.285 g, 16.5 mmol, 55% yield). The product was characterized as follows: 1H-NMR (400 MHz, CDCl3) δ: 8.62 (t, 1H, J = 1.4 Hz), 8.53 (s, 2H, J = 1.4 Hz), 3.94 (s, 6H); 13C-NMR (100 MHz, CDCl3) δ: 165.2 (2C), 142.9 (2C), 132.6 ( 2C), 130.2, 93.8, 53.1 (2C); MS (EI) m/z: 320 (M+); HRMS (EI) calculated for C10H9IO4: 319.9546, found: 319.9553; Elemental analysis calculated for C10H9O4: C, 37.52; H, 2.83; found: C, 37.44; H, 2.86.
