Synthesis
a) 2,6-Dichloroisonicotinic acid (200 g, 1.04 mol) was dissolved in methanol (3 L) and 32% aqueous sodium hydroxide solution (770 mL) was added. The stirred mixture was heated to 34°C, then warmed to 70°C and kept at this temperature for 4 hours of reaction. After the reaction was completed, it was cooled to room temperature. The reaction mixture was neutralized with 32% aqueous hydrochloric acid solution (100 mL) and 25% aqueous hydrochloric acid solution (700 mL). The mixture was stirred at room temperature overnight. The white precipitate formed was collected by filtration, washed with methanol and dried. The filtrate was evaporated and the residue was suspended in water (200 mL). The resulting mixture was heated to 60 °C and the solid product was collected, washed with water and dried. All products were combined to give 2-chloro-6-methoxyisonicotinic acid (183 g) as a white solid; LC-MS: t R = 0.80 min, [M + 1] + = 187.93.
References
[1] Tetrahedron, 2002, vol. 58, # 34, p. 6951 - 6963
[2] Organic Letters, 2000, vol. 2, # 22, p. 3421 - 3423
[3] Patent: WO2011/7324, 2011, A1. Location in patent: Page/Page column 20
[4] Patent: US2012/108638, 2012, A1. Location in patent: Page/Page column 8
[5] Patent: US2013/303514, 2013, A1. Location in patent: Paragraph 0192
