2-Chloro-3-Methyl-4-pyridinecarboxylic Acid

Uses

2-Chloro-3-methylisonicotinic Acid is a derivative of Isonicotinic Acid (I821760) and is used as a reagent in the synthesis of N-pyridinylmethyl benzamide derivatives as anticancer agents.

Synthesis

Step 3: Synthesis of 2-chloro-3-methylpyridine-4-carboxylic acid A mixture of 2-chloro-N,3-dimethyl-N-phenylpyridine-4-carboxamide (2.2 g, 8.5 mmol) was mixed with a mixture of concentrated H2SO4 (23.2 mL) and water (16.8 mL), which was subsequently heated to 130 °C and kept for 46 hours. Upon completion of the reaction, the reaction mixture was cooled to room temperature and poured into ice (200 mL) and stirred until the ice was completely melted. The mixture was adjusted to alkaline (pH 8) by batchwise addition of solid Na2CO3 (50.3 g). The suspension was filtered and the filtrate was acidified to pH 3 by the addition of 6 M HCl (aq) (ca. 1.5 mL).The resulting solid was collected by filtration, washed with water (20 mL) and dried under vacuum at 40 °C for 10 h to afford 2-chloro-3-methyl-4-pyridinecarboxylic acid (779 mg, 54%) as a pink solid.LC-MS purity 100%, m/z = 171.9, 173.9; 1H NMR (500 MHz, MeOD) δ ppm 8.30 (d, J = 4.89 Hz, 1H), 7.64 (d, J = 5.04 Hz, 1H), 2.58 (s, 3H).

References

[1] Tetrahedron, 1991, vol. 47, # 9, p. 1697 - 1706
[2] Patent: WO2012/142513, 2012, A1. Location in patent: Page/Page column 427-428