38367-36-1

67643-17-8

38367-36-1

Step 3: Synthesis of 2,4-dichloro-6-methylnicotinonitrile from 2,4-dihydroxy-6-methylnicotinonitrile: 2,4-dihydroxy-6-methylnicotinonitrile (40 g, 266.4 mmol) was dissolved in phosphorus trichloride (POCl3, 120 ml) and N,N-dimethylformamide (DMF, 4 drops) was added as catalyst. The reaction mixture was heated to reflux and maintained for 3 hours. Upon completion of the reaction, the excess POCl3 was removed by distillation under reduced pressure. the residue was dissolved in ethyl acetate (EtOAc, 2 L) and neutralized by slow addition of saturated aqueous sodium bicarbonate (NaHCO3). The neutralized mixture was filtered through diatomaceous earth to remove insoluble impurities, the organic layer was separated and dried with anhydrous sodium sulfate (Na2SO4). Finally, 2,4-dichloro-6-methylnicotinonitrile was obtained by concentration under reduced pressure as an off-white solid (45 g, 90% yield).