1-Cyclopropyl-4-oxo-cyclohexanecarbonitrile

Synthesis

The general procedure for the synthesis of 1-cyclopropyl-4-oxocyclohexanecarbonitrile using 8-cyclopropyl-1,4-dioxaspiro[4.5]decane-8-carbonitrile (compound of formula 3) as starting material was as follows: the compound of formula 3 (103.5 g, 0.5 mol) was dissolved in dichloromethane (1000 mL) and cooled down to 0 °C. The reaction was completed with the addition of trifluoroacetic acid (100 mL). Under stirring, trifluoroacetic acid (100 mL) was slowly added, keeping the reaction temperature at 0 °C. The reaction process was monitored by thin layer chromatography (TLC) until the feedstock completely disappeared. Upon completion of the reaction, the reaction mixture was poured into saturated sodium bicarbonate solution and the organic phase was extracted with dichloromethane. The organic phases were combined and concentrated by rotary evaporator to remove the solvent to give the crude product. The crude product was recrystallized by petroleum ether to give colorless needle-like crystals of 1-cyclopropyl-4-oxocyclohexanecarbonitrile (compound of formula 4, 75.6 g, 92.8% yield).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 5, p. 1446 - 1450
[2] Patent: CN106467477, 2017, A. Location in patent: Paragraph 0031; 0032; 0033
[3] Patent: US2007/299080, 2007, A1. Location in patent: Page/Page column 43