The general procedure for the synthesis of 4-cyanotetrahydropyran from tetrahydropyran-4-carboxamide was as follows: thionyl chloride (10.0 mL, 137 mmol) was slowly added to tetrahydropyran-4-carboxamide (3.0 g, 23 mmol), and the reaction mixture was stirred under reflux for 4 hr. Upon completion of the reaction, the mixture was carefully decanted onto ice and the pH was adjusted with 50% sodium hydroxide solution to 14. Subsequently, the aqueous phase was extracted with ethyl acetate (3 x 50 mL), the organic phases were combined and dried over anhydrous sodium sulfate. The organic phase was concentrated under reduced pressure to give a light yellow oily product (2.4 g, 94% yield) which did not require further purification. The structure of the product was confirmed by the following characterization data: IR (νmax, cm-1 ): 2961, 2932, 2851, 2240, 1468, 1446, 1390, 1242, 1125, 1066, 1011; 1H NMR (500 MHz, CDCl3): δ 3.91 (2H, ddd, J = 11.9, 6.3, 3.6 Hz, 2 × 3.6 Hz, 2 × 3.6 Hz, 2 × 3.9, 6.3, 3.6 Hz, 2 × 3.6 Hz). 3.6 Hz, 2×2-HA), 3.61 (2H, ddd, J = 11.9, 7.8, 3.3 Hz, 2×2-HB), 2.91-2.85 (1H, m, 4-H), 1.99-1.92 (2H, m, 2×3-HA), 1.91-1.84 (2H, m, 2×3-HB); 13C NMR (75 MHz, CDCl3): δ 121.2, 65.6, 28.9, 25.3; HRMS (ESI+): calculated value C6H10NO ([M+H]+): 112.0756, measured value: 112.0754, Δ -1.8 ppm.
