Synthesis
Step 1: 6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (45.0 g, 335 mmol) was added to phosphorochloridic acid (652 g, 4250 mmol) and the reaction was stirred at 130°C for 2 hours. After the reaction was completed, the reaction solution was concentrated and the resulting residue was dissolved in dichloromethane and the pH was adjusted to 8 by slowly adding 4 M aqueous sodium hydroxide.The organic layer was separated, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure to give 2-chloro-6-methylnicotinonitrile (51.0 g, 99% yield).1H NMR (400 MHz, CDCl3) δ 2.65 (s, 3H), 7.24 (d, J = 8.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H).
References
[1] Patent: US2017/145005, 2017, A1. Location in patent: Paragraph 0149; 0150; 0151; 0152
[2] Heterocycles, 1995, vol. 41, # 6, p. 1307 - 1318
[3] Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 6, p. 2206 - 2210
[4] Polish Journal of Chemistry, 1982, vol. 56, # 2, p. 419 - 423
[5] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2014, vol. 69, # 5, p. 509 - 518
