2-Hydroxyisonicotinic acid

Synthesis

90 mL of concentrated hydrochloric acid was slowly added to 5.00 g (31.7 mmol) of 2-chloroisonicotinic acid. The suspension was heated to 140-150 °C (oil bath). The resulting reaction mixture gradually became a clear solution after heating, but returned to a suspension after 24 hours. Another 20 mL of hydrochloric acid was added to the reaction system, and the mixture became clear. Heating continued for another 24 hours. Then, another 20 mL of hydrochloric acid was added, and the reaction mixture was heated for another 12 hours. The mixture was cooled in an ice bath, during which solid precipitation was observed. The reaction mixture was diluted with an equal volume of ice water and filtered. The filter cake was washed with cold water, and the precipitate was dried under high vacuum to obtain pure 2-hydroxyisonicotinic acid as a white solid, yielding 3.92 g (89%).

Figure 2: Synthetic Route of 2-Hydroxyisonicotinic Acid

Chemical Properties

White powder

Uses

Used in the synthesis of selective inhibitors of neuropeptide Y Y5 inhibiting food intake. Also used in the optimization of p-subsite residues of HIV protease inhibitors.

Synthesis Reference(s)

Tetrahedron Letters, 29, p. 4389, 1988 DOI: 10.1016/S0040-4039(00)80502-X