Synthesis
General procedure for the synthesis of 2-chloronicotinamide from 2-chloro-3-cyanopyridine: 400 mL of concentrated sulfuric acid was added to a 1000 mL three-necked flask, followed by the addition of 2-chloro-3-cyanopyridine (138 g, 1 mol), which was stirred until completely dissolved. The reaction system was warmed up to 90 °C and the reaction was maintained at this temperature with stirring for 2 hours. Upon completion of the reaction, the reaction mixture was slowly poured into a mixture containing 1000 mL of ammonia and 1 kg of ice and stirring was continued for 1 hour. The precipitated crude product was collected by filtration. The crude product was transferred to 1000 mL of ethyl acetate and stirred for 1 hour to wash and subsequently separated by filtration to give a white solid product. Finally, the white solid was dried by blowing at 50 °C to give 153 g of the intermediate 2-chloronicotinamide as a white solid in 98% yield.
References
[1] Patent: CN105367571, 2017, B. Location in patent: Paragraph 0014; 0037; 0038
[2] Tetrahedron Letters, 2012, vol. 53, # 4, p. 449 - 452
[3] Journal of Chemical Research, 2011, vol. 35, # 8, p. 480 - 483
[4] Synlett, 2018, vol. 29, # 15, p. 2061 - 2065
[5] Journal of Organic Chemistry, 1954, vol. 19, p. 1633,1636