4-Chloro-2-Methoxy-3-nitropyridine

165547-79-5

74-88-4

934180-48-0

The general procedure for the synthesis of 4-chloro-2-methoxy-3-nitropyridine from 2-hydroxy-3-nitro-4-chloropyridine and iodomethane was as follows: iodomethane (2.06 mL, 32.99 mmol) was slowly added to a suspension of 4-chloro-2-hydroxy-3-nitropyridine (2.87 g, 16.49 mmol) (for preparation, see Bioorg. Med. . chem. lett., 2003, 13, 125). The reaction mixture was heated with stirring at 85°C for 3.5 hours. Subsequently, a solution of sodium carbonate (16.49 mmol) in toluene (100 mL) was added to the reaction system and heating was continued. After the reaction mixture was cooled to room temperature, it was filtered through a diatomaceous earth pad and the solids were washed with toluene. The filtrate and washings were combined and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography using ethyl acetate:heptane (1:9, v/v) as eluent. The target fraction was collected and concentrated under reduced pressure to give the white solid product 4-chloro-2-methoxy-3-nitropyridine (1.99 g, 64% yield). Product characterization data: MS (ESI) m/z: 189/191 ([M + H]+).