[Synthesis]
General procedure for the synthesis of 2,4-dimethoxypyridine from 2,4-dichloropyridine and sodium methanol: Freshly prepared sodium methanol (24 g, 0.44 mol) was added to an anhydrous N-methyl-2-pyrrolidinone (80 mL) solution of 2,4-dichloropyridine (15 g, 0.10 mol). The reaction mixture was stirred at 120 °C for 6 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (800 mL) and washed with water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give 2,4-dimethoxypyridine (4) as a colorless oil which was pure enough to be used in the next step. Yield: 11.2 g (80%).1H NMR (400 MHz, DMSO-d6): δ 3.80 (s, 3H), 3.84 (s, 3H), 6.33 (d, J = 2.0 Hz, 1H), 6.60 (dd, J = 2.0 Hz, J = 5.6 Hz, 1H), 7.97 (d, J = 5.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ 167.5, 165.4, 147.4, 106.1, 93.8, 55.3, 53.1; HRMS (ESI) m/z calcd for C7H10NO2 [M+H]+: 140.0706; found: 140.0707. |