4-Amino-2-methoxypyridine

14432-12-3

20265-39-8

General procedure for the synthesis of 4-amino-2-methoxypyridine from 2-chloro-4-aminopyridine: 4-amino-2-chloropyridine (15 g, 117 mmol, 1.0 equiv) was dissolved in 100 mL of tetrahydrofuran (THF). To this solution was added a methanolic solution of sodium methanolate (1.0 M, 234 mL, 234 mmol, 2.0 eq.), and the mixture was subsequently transferred to a sealed tube and the reaction was refluxed for 16 hours at 140 °C. Upon completion of the reaction, the reaction mixture was slowly poured into 500 mL of rapidly stirred saturated aqueous sodium bicarbonate solution. The organic and aqueous layers were separated by adding 500 mL of ethyl acetate for extraction. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent. Finally, purification by silica gel column chromatography (eluent: 30% hexane solution of ethyl acetate) gave the target product 4-amino-2-methoxypyridine (2.1 g, 14% yield) as a yellow solid.