Acetamide → 2-Amino-6-chloronicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2,6-dichloronicotinic acid (36 g), acetamide (80 g), potassium carbonate (78 g), copper(I) chloride (0.93 g), and xylene (80 mL) was added tris(2-(2-methoxyethoxy)ethyl)amine (3.0 mL), which was stirred overnight at 145° C. The reaction mixture was cooled to room temperature, after which copper(I) chloride (0.46 g) was added to the reaction mixture at the same temperature, and then stirred overnight at 145° C. The reaction mixture was cooled to 105° C., after which water (100 mL) was added at the same temperature, and then stirred for 1 hour at the same temperature. The reaction mixture was cooled to room temperature, 5N hydrochloric acid (150 mL) was added thereto at the same temperature, and then the reaction mixture was neutralized with an aqueous citric acid solution. Ethyl acetate was added to the reaction mixture, which was filtered through Celite. The organic layer was washed with saturated brine, after which the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate), after which recrystallization was performed from an ethyl acetate-hexane system to obtain the titled compound (1.4 g).

Provenance & Evidence