5470-22-4

White solid

4-Chloropicolinic Acid is a reactant used in the synthesis of VU0431316, a negative allosteric modulator of mGlu5.

General procedure for the synthesis of 4-chloropyridine-2-carboxylic acid from 2-pyridinecarboxylic acid: a suspension of 2-pyridinecarboxylic acid (0.79 g, 6.35 mmol) and sodium bromide (1.30 g, 12.7 mmol) in 10 mL of thionyl chloride was heated for 20 hr under mild reflux conditions. During the reaction, the initial dark green color of the mixture gradually changed to a deep red color. Upon completion of the reaction, the excess thionyl chloride was removed by rotary evaporation, and the resulting orange residue was dissolved in about 15 mL of dichloromethane and filtered through diatomaceous earth to remove insoluble impurities. The orange filtrate was cooled to -2°C and 20 mL of double-distilled water was slowly added under vigorous stirring while maintaining the reaction temperature between -2 and 2°C. At this point, the color of the solution changed to light orange and a white precipitate was produced. Subsequently, the mixture was continued to be stirred at room temperature for 20 hours. Afterwards, dichloromethane and water were removed by rotary evaporation. Finally, the solid product was recrystallized from a minimal amount of ethanol to give 0.28 g (28% yield) of 4-chloropyridine-2-carboxylic acid. The structure of the product was confirmed by 1H NMR (DMSO-d6): δ= 8.72 (1H, d, J = 4.9 Hz), 8.09 (1H, d, J = 1.6 Hz), 7.84 (1H, dd, J = 4.9, 1.6 Hz).

[1] Patent: WO2008/17855, 2008, A1. Location in patent: Page/Page column 48-49
[2] Patent: WO2008/17855, 2008, A1. Location in patent: Page/Page column 48-49
[3] Synthetic Communications, 1996, vol. 26, # 10, p. 2017 - 2025
[4] Patent: US2006/160803, 2006, A1. Location in patent: Page/Page column 136
[5] Patent: EP1650194, 2006, A1. Location in patent: Page/Page column 37