Acetamide → 2-Amino-6-chloronicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2,6-dichloronicotinic acid (40 g (purity: 90%), 0.19 mol), acetoamide (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) was added tris(2-(2-methoxyethoxy)ethyl)amine (3.0 mL, 9.4 mmol), which was stirred overnight at 145° C. After allowing to cool on standing, to the reaction mixture was added copper (I) chloride (0.46 g, 4.6 mmol), followed by stirring overnight at 145° C. After cooling the reaction mixture to 105° C., water (100 mL) was added followed by stirring for 1 hour at the same temperature and allowing to cool to room temperature on standing. After neutralizing the reaction mixture with 5 N hydrochloric acid (150 mL) and aqueous citric acid, ethyl acetate was added. This mixture was filtered through Celite. After separating the organic phase and washing with sat. NaCl, the solvent was concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from an ethyl acetate-hexane system to obtain the title compound (1.4 g, 8.3 mmol, 4.5%) as white crystals.

Provenance & Evidence