Synthesis
General procedure for the synthesis of 4-hydroxy-2-methylpyridine from 2-methyl-4-aminopyridine:
[0220] To an aqueous solution (75 mL) containing 2-methylpyridin-4-amine (10.2 g, 94 mmol) and nitric acid (56.5 mL, 1,273 mmol) was slowly added a solution of sodium nitrite solution (9.44 g, 137 mmol) in water (38 mL) over a period of 25 minutes at 0 °C while maintaining vigorous stirring. The reaction mixture was continued to be stirred at 0 °C for 30 min, followed by transfer to a refrigerator at -17 °C for overnight storage. Upon completion of the reaction, the mixture was filtered and the solid product was collected and dried under vacuum to afford 2-methylpyridin-4-ol (6.5 g, 59.6 mmol, 63.2% yield) as a beige solid. The product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 2.53-2.60 (m, 3H), 7.01-7.17 (m, 2H), 8.36-8.49 (m, 1H). Mass spectrometry analysis showed a measured value of 110.1 for [M + H]+.
References
[1] Patent: WO2011/146287, 2011, A1. Location in patent: Page/Page column 59
[2] Archiv der Pharmazie (Weinheim, Germany), 1958, vol. 291, p. 429,434
[3] Roczniki Chemii, 1957, vol. 31, p. 1147,1151
[4] Chem.Abstr., 1958, p. 10072
[5] Journal of Chemical Thermodynamics, 1982, vol. 14, # 1, p. 45 - 50
