Acetamide → 2-Amino-6-chloronicotinic acid

Temperature

145 °C

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.

1. temperatureAfter cooling
2. stirringwas stirred overnight at 145° C
3. temperatureAfter cooling the reaction solution to 105° C.
4. stirringthe solution was stirred for 1 hour at the same temperature
5. temperaturecooled down to room temperature
6. filtrationthe solution was filtered through Celite pad
7. washThe organic layer was washed with brine
8. customthe solvent was evaporated in vacuo
9. customThe residue was purified by silica gel column chromatography (ethyl acetate), recrystallization by the ethyl acetate-hexane

ORD record

ord-610168b699c54c9cb7f2d01cd5b18c58

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932272B2