At 0 °C, n-butyllithium (1.67 M hexane solution, 2.9 mL, 4.8 mmol) was slowly added dropwise to a tetrahydrofuran (THF, 5 mL) solution of 1,3-dimethoxybenzene (0.55 g, 4.0 mmol). After the reaction mixture was stirred at 0 °C for 2 h, N,N-dimethylformamide (DMF, 0.34 mL, 4.4 mmol) was added and stirring was continued at 0 °C for 2 h. The reaction mixture was then mixed with N,N-dimethylformamide (DMF, 0.34 mL, 4.4 mmol). Subsequently, ammonia solution (8 mL, 120 mmol) and dihydroammonium iodide (DIH, 0.91 g, 2.4 mmol) were added to the reaction system and the mixture was transferred to room temperature and stirred for 2 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium sulfite solution (15 mL) and then extracted with ether (3 x 20 mL). The organic layers were combined, washed with brine and dried over anhydrous sodium sulfate. The crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=3:1) to afford pure 2,6-dimethoxybenzonitrile in 94% yield as a colorless solid.
