General procedure for the synthesis of 2-chloro-4,6-dimethylpyridine from 2-amino-4,6-dimethylpyridine: A mixture of 2-amino-4,6-dimethylpyridine (90 g, 0.736 mol) and sodium chloride (216 g, 3.69 mol) in concentrated hydrochloric acid (720 mL) was cooled to -15 to -20°C. A solution of sodium nitrite (71.2 g, 1.03 mol) in water (135 mL) was added slowly and dropwise over 30 minutes. Subsequently, additional sodium chloride (216 g, 3.69 mol) was added and the reaction mixture was gradually warmed to room temperature with continuous stirring for 1 hour. Upon completion of the reaction, the reaction mixture was neutralized with solid sodium bicarbonate (700 g) and then extracted with dichloromethane (1 L). The extract was filtered and the organic and aqueous phases were separated. The organic phase was concentrated under reduced pressure and the resulting crude product was purified by fast column chromatography on silica gel (100-200 mesh), using a petroleum ether solution of 20% dichloromethane as eluent, to give 2-chloro-4,6-dimethylpyridine (40 g, 38% yield) as a final solid product.
