2-Cyanotetrahydrofuran

Synthesis

General procedure for the synthesis of 2-cyanotetrahydrofuran from tetrahydrofuran-2-carboxamide: Preparation of 2-cyanotetrahydrofuran. Trifluoroacetic anhydride (1.55 g, 7.38 mmol) was slowly added to an anhydrous 1,4-dioxane (10 mL) ice-cold solution (0 °C) of tetrahydrofuran-2-carboxamide (0.77 g, 6.71 mmol) and pyridine (1.06 g, 13.42 mmol) at a rate of one drop every 10 seconds. The addition of trifluoroacetic anhydride was monitored to ensure that the internal temperature was below 5 °C and that the addition was completed within 20 min. The reaction mixture was gradually warmed to room temperature and stirred continuously for 3 hours. Upon completion of the reaction, chloroform (100 mL) was added to the mixture and extracted sequentially with water (30 mL) and saturated aqueous sodium chloride solution (20 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by fast column chromatography (eluent: hexane to 25% ethyl acetate/hexane gradient elution) to afford 2-cyanotetrahydrofuran (0.51 g, 62% yield) as a colorless oil.1H NMR (CDCl3, 300 MHz) δ: 4.70 (1H, m), 3.96 (2H, m), 2.24 (2H, m), 2.08 (2H, m). m).

References

[1] Patent: US2005/187266, 2005, A1
[2] Patent: WO2004/92145, 2004, A1. Location in patent: Page 137