6-Chloro-1-methyl-2(1H)pyridinone

16879-02-0

74-88-4

17228-63-6

The general procedure for the synthesis of 6-chloro-1-methylpyridin-2(1H)-one from 6-chloropyridin-2-ol and iodomethane was as follows: to a solution of 6-chloropyridin-2-ol (10.00 g, 77.19 mmol) in acetone (350 mL) was added potassium carbonate (K2CO3, 37.34 g, 270.2 mmol) and iodomethane (17.37 ml. 270.2 mmol). The reaction mixture was stirred at room temperature for 1 hour and then under reflux conditions for 16 hours. Upon completion of the reaction, the mixture was cooled to room temperature, filtered to remove the potassium carbonate and the solid was washed with acetone. The filtrate was concentrated and the residue partitioned between water (H2O) and dichloromethane (CH2Cl2). The organic and aqueous phases were separated and the aqueous phase was extracted once more with dichloromethane (1x). The organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated to give a yellow oily crude product. The crude product was purified by silica gel fast column chromatography using 10:1 dichloromethane/ethyl acetate (CH2Cl2/EtOAc) as eluent. The final target product 6-chloro-1-methylpyridin-2(1H)-one (7.38 g, 67% yield) was obtained as a white solid. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3) and LRMS (ESI pos): 1H-NMR δ 7.23 (dd, 1H), 6.50 (dd, 1H), 6.30 (m, 1H), 3.69 (s, 3H); LRMS (ESI pos) m/e 144 (M + 1).