4-Chloro-3-methoxy-2-methylpyridine

76015-11-7

107512-34-5

General procedure for the synthesis of 4-chloro-3-methoxy-2-methylpyridin-4-one from 3-methoxy-2-methyl-1H-pyridin-4-one: 3-methoxy-2-methyl-4(1H)-pyridinone (27.8 g, 0.2 mol) was added to phosphorus trichloride (200 mL), and the mixture was heated and refluxed for 18 hr at 90°C under nitrogen protection. Upon completion of the reaction, the homogeneous mixture was cooled to 20°C and subsequently concentrated under reduced pressure. The concentrated residue was dissolved in ice water and the pH was adjusted to 12 with 40% sodium hydroxide solution, at which point a turbid suspension appeared. Extraction was carried out with dichloromethane (3 x 100 mL) and the organic phases were combined and washed with water. The organic phase was dried over anhydrous magnesium sulfate and the dichloromethane was removed by rotary evaporation to afford the target product 4-chloro-3-methoxy-2-methylpyridine (30.2 g, 96% yield). The product was characterized by 1H NMR (CDCl3): δ 8.14 (d, 1H, J = 5.32 Hz), 7.17 (d, 1H, J = 5.10 Hz), 3.85 (s, 3H), 2.54 (s, 3H). The mass spectrum (ESI) showed a m/z of 157.91 ([M+H]+).