[Synthesis]
Step 8. Preparation of 4-chloro-6-methylnicotinonitrile (B17-8): B17-7 (20 g, 131.5 mmol) was suspended in phosphorus trichloride (POCl3, 62 mL, 580 mmol) and heated at 110 °C for 15 minutes. After the reaction mixture was cooled to 25 °C, phosphorus pentachloride (PCl5, 38.12 g, 183.4 mmol) was added in batches over 20 min. Subsequently, the mixture was heated at 110 °C for 1 h and then concentrated. The resulting residue was diluted with ethyl acetate (EtOAc, 100 mL), cooled to 10 °C and quenched with sodium carbonate (Na2CO3, 200 mL, aqueous solution). The mixture was extracted with ethyl acetate (3 x 250 mL), the organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography using a petroleum ether solution of 4-5% ethyl acetate as eluent to give B17-8 as an off-white fluffy solid. Yield: 7.5 g, 37%. 1H NMR (CDCl3): δ 8.75 (s, 1H), 7.38 (s, 1H), 2.65 (s, 3H). Mass spectrum: (M + 1) 153, calculated value C7H5ClN2. |