To a solution of 3,4-dimethoxybenzaldehyde (2.00 g, 12.0 mmol) in EtOH (100 mL) was added iodine (3.65 g, 14.4 mmol) and silver sulfate (4.49 g, 14.4 mmol) under nitrogen and the mixture was stirred for 3 hours at room temperature. The solvent was removed, water was added and the mixture was extracted with DCM. The organic extract was washed with brine, dried with sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by fast chromatography using petroleum ether/ethyl acetate 2:1 (v:v) as eluent to give 2-iodo-4,5-dimethoxybenzaldehyde (2.81 g, 80%).LC-MS (ES-API); 8.52 min at room temperature; m/zC9H9IO3[M+H]+ calculated value 293.0, measured value 293.0.
At 0C. , a solution of KMnO4 (0.76 g, 4.79 mmol) in water (15 mL) was added dropwise to a stirred solution of 2-iodo-4,5-dimethoxybenzaldehyde (1.0 g, 3.42 mmol) in CH3CN (25 mL). The resulting mixture was stirred at room temperature overnight. After completion of the reaction, the pH was adjusted to <7 with 1 NHCl. The mixture was extracted with DCM, the organic layers were combined, washed with brine, dried over sodium sulfate, and evaporated to give 4,5-dimethoxy-2-iodobenzoic acid (0.89 g, 85%).
