Acetamide → 2-Amino-6-chloronicotinic acid

Participants

Reaction Conditions

Reaction Steps

Tris(2-(2-methoxyethoxy)ethyl)amine (3.0 mL, 9.4 mmol) was added to a mixture of 2,6-dichloronicotinic acid (40 g (90% purity), 0.19 mol), acetamide (80 g, 1.4 mol), potassium carbonate (78 g, 0.56 mol), copper(I) chloride (0.93 g, 9.4 mmol) and xylene (80 mL), which was stirred overnight at 145° C. After cooling, copper(I) chloride (0.46 g, 4.6 mmol) was added to the reaction solution, which was stirred overnight at 145° C. After cooling the reaction solution to 105° C., water (100 mL) was added, the solution was stirred for 1 hour at the same temperature, and cooled down to room temperature. 5N hydrochloric acid (150 mL) was added, the solution was neutralized with a citric acid aqueous solution, then, ethyl acetate was added, and the solution was filtered through Celite pad. The organic layer was washed with brine, then, the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate), recrystallization by the ethyl acetate-hexane was carried out to obtain the title compound (1.4 g, 8.3 mmol, 4.5%) as white crystal.

Provenance & Evidence