The general procedure for the synthesis of 3-cyano-2,5,6-trifluoropyridine from 3-cyano-2,6-dichloro-5-fluoropyridine was as follows: 2,6-dichloro-5-fluoronicotinonitrile (25.67 g, 134 mmol) was mixed with spray dried potassium fluoride (23.6 g, 406 mmol) (Aldrich) by freshly milling the mixture in air to remove agglomerates and then mixing with thorough shaking. Ensure that the two are completely mixed before adding dry dimethyl sulfoxide (30 mL). The mixture was effectively stirred at room temperature under argon protection for 1-2 min, followed by transfer to a 100°C oil bath for 5 min. The temperature was then raised to 130 °C within 10 min and stirring was continued at this temperature for 40 min. The reaction process was monitored by NMR spectroscopy, which showed a conversion of 86% after 10 minutes of reaction at 130 °C and over 95% after 40 minutes. Upon completion of the reaction, the viscous purple mixture was cooled to room temperature, shaken with dichloromethane (30 mL) in an ice bath, and subsequently upsampled directly onto a fast silica gel column (silica gel 1.0 kg; column size 120 mm × 0.6) that was pre-equilibrated with dichloromethane. Elution with dichloromethane (140 mL of fractions were collected; combined fractions 10-19) afforded 20.65 g of a clarified light amber oily product.NMR analysis showed the product, 3-cyano-2,5,6-trifluoropyridine, to be in a molar ratio of 1:0.58 to dimethylsulfoxide (16.0 g of 3-cyano-2,5,6-trifluoropyridine; 76% yield).1H-NMR (300 MHz, CDCl3) was used for the analysis. MHz, CDCl3) δ 7.99 (m, 1H).LC/MS (ESI): calculated mass 158.0, measured value 159.5 (MH)+.
