Example 1 Synthesis of 3-cyclopropyl-3-oxopropanenitrile: To a mechanically stirred solution of 15.0 g (176 mmol) of cyanoacetic acid and 100 mg of 1,10-phenanthroline dissolved in 500 mL of THF was slowly added 141 mL (352 mmol) of 2.5 M n-butyllithium in hexane solution at -78 °C. The reaction system was slowly warmed to 0°C in a water bath and held for 15 minutes until most of the brown color faded. Subsequently, the mixture was re-cooled to -78 °C and 8.0 mL (88 mmol) of cyclopropylcarbonyl chloride dissolved in 8 mL of THF was added dropwise. The reaction mixture was gradually warmed to room temperature and stirring was continued for 15 minutes. The reaction solution was poured into 300mL of 5% HCl aqueous solution and extracted three times with ether. The organic phases were combined, washed sequentially with saturated aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, it was purified by silica gel column chromatography using a hexane solution of 30% ethyl acetate as eluent to give 6.5 g (54% yield) of the target product 3-cyclopropyl-3-oxopropanenitrile. The product was stored with 1% w/w BHT in 40 mL of dichloromethane at -5 °C. TLC detection (20% ethyl acetate/hexane, Rf 0.12) showed green coloration with ninhydrin staining; 1H-NMR (300 MHz, CDCl3): δ 3.63 (s, 2H), 2.10 (m, 1H), 1.20 (m, 2H), 1.10 (m, 2H).
