2,3-dichloro-6-methoxypyridine

34392-85-3

83732-68-7

The general procedure for the synthesis of 2,3-dichloro-6-methoxypyridine from 2-chloro-3-amino-6-methoxypyridine was as follows: 3-amino-2-chloro-6-methoxypyridine (500 mg, 3.17 mmol) was dissolved or suspended in a conical flask. Hydrochloric acid (10 mL) was stirred at -5°C while an aqueous solution of sodium nitrite (1.09 g, 15.82 mmol) was added slowly and dropwise (5 mL) over 10 minutes. After continuing to stir the reaction mixture for 10 min, copper chloride (3.13 g, 31.65 mmol) was added in batches over 5 min. The reaction mixture was stirred at -5 °C for 20 min, after which the cooling bath was removed and the mixture was allowed to continue stirring for 3 h at room temperature. Upon completion of the reaction, the mixture was diluted with distilled water (100 mL), the pH was adjusted to 10-11 with 5N aqueous sodium hydroxide solution, and then extracted with ether (3 x 50 mL). The organic phases were combined, washed with saturated saline, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography with the eluent of ethyl acetate:heptane (1:9, v/v) to afford the target product 2,3-dichloro-6-methoxypyridine as a light yellow oil (229 mg, 41% yield). The product was analyzed by mass spectrometry (ESI), m/z: 178 ([M + H]+).