Synthesis
General procedure for the synthesis of 5-cyanofuran-2-carboxylic acid from 5-formylfuran-2-carboxylic acid: to a solution of 2-formyl-5-furancarboxylic acid (0.28 g, 2.0 mmol) in pyridine (5.0 mL) was added hydroxylamine hydrochloride (NH2OH-HCl) (0.27 g, 4.0 mmol). The mixture was heated to 85 °C, followed by the addition of acetic anhydride (4.0 mL). The reaction mixture was stirred at 85 °C for 3 h. The mixture was cooled to 60 °C and poured into water (25 mL). The mixture was cooled to room temperature and stirred overnight (the pH of the solution was measured to be 5-6). Impurities were extracted with a 4:1 dichloromethane/isopropanol mixture (3 x 30 mL). The aqueous layer was alkalized with a 2 N sodium hydroxide solution to a pH of about 9, and the pyridine was again extracted with a 4:1 dichloromethane/isopropanol mixture (3 x 30 mL). The aqueous solution was subsequently acidified to pH about 2 and the product was extracted with a 3:1 dichloromethane/isopropanol mixture (3 x 50 mL). The organic extracts were combined, dried over anhydrous magnesium sulfate and the solvent was evaporated to give the pure product as a light brown solid in 90% yield. NMR hydrogen spectrum (DMSO-d6): δ 13.80 (broad single peak, 1H), 7.75 (double peak, 1H), 7.40 (double peak, 1H). IR spectrum (pure): 3200, 2250, 1053, 1025, 1006 cm-1.
References
[1] Patent: WO2004/96795, 2004, A2. Location in patent: Page 25-26
[2] Patent: WO2007/123516, 2007, A1. Location in patent: Page/Page column 34
[3] Patent: US2008/51402, 2008, A1. Location in patent: Page/Page column 44
[4] Patent: WO2007/48088, 2007, A2. Location in patent: Page/Page column 82-83
[5] Patent: WO2006/47504, 2006, A1. Location in patent: Page/Page column 36
