Benzylamine → N3-Benzyl-2-chloronicotinamide

Participants

Reaction Conditions

Reaction Steps

2-Chloronicotinic acid (25 grams, 158.67 mmol) is placed into a 2L 4-neck round bottom flask equipped with mechanical stirring, thermometer, nitrogen inlet and a rubber septum and is charged with 800 ml of tetrahydrofuran (THF). The reaction is chilled to 0° C. N-methylmorpholine (16.05 grams, 158.67 mmol) is added via syringe. The reaction is chilled to -10° C. and isobutyl chloroformate (21.67 grams, 158.67 mmol) is added to the reaction via syringe while maintaining the temperature at less than 0° C. The reaction is allowed to stir at -10° C. for 30 minutes. Benzylamine (18.70 grams, 174.54 mmol) is then added via syringe while maintaining the temperature below 0° C. The reaction is allowed to slowly warm to room temperature. After stirring for 18 hours IN HCl (300 ml) is added to the reaction. This is then extracted with ethyl acetate (2×350 ml). The organics are combined and washed with 1N HCl (1×300 ml) and 12% sodium hydroxide (2×300 ml). The organic layer is dried over anhydrous magnesium sulfate, filtered and concentrated to a white paste. The paste is triturated with diethyl ether to yield a solid. This is filtered and washed with diethyl ether (2×65 ml). The filtrates are concentrated and triturated with fresh diethyl ether to yield a second crop of compound which is combined with the first to yield 28.11 grams (71.8%) of N-benzyl-2-chloronicotinamide as a white crystalline solid.

Provenance & Evidence