Example 11B Synthesis of 5-bromo-2-chloro-3-methylpyridine: The product of Example 11A, 5-bromo-3-methylpyridin-2-one (4.1 g, 22.18 mmol), was dissolved in DMF (40 mL) and phosphoryl chloride (10 g, 65.4 mmol) was added drop-wise at 0 °C. The reaction mixture was heated at 120 °C for 2 hours. Upon completion of the reaction, the mixture was cooled to room temperature and carefully poured into an ice/water mixture. The mixture was adjusted to alkaline with NH4OH, the precipitate was collected by filtration and the filter cake was washed with ice water. The resulting solid was dissolved in dichloromethane (100 mL), the organic layer was washed with brine and dried with anhydrous MgSO4. The dried solution was filtered through a silica pad and the filtrate was concentrated to give 2-chloro-3-methyl-5-bromopyridine as a white solid (3.48 g, 78% yield). The product was characterized by 1H NMR (CDCl3, 300MHz): δ 2.39 (s, 3H), 7.70 (m, 1H), 8.31 (d, J = 3Hz, 1H).
