反应详情

温度

0 °C

Solid KHMDS (3.48 g, 17.5 mmol) is dissolved in THF (20.0 mL) and cooled to 0° C. Cyclobutanecarbonitrile (1.42 g, 17.5 mmol) is added, and the resulting solution stirred for 40 minutes. A solution of 4-fluorobenzonitrile (2.12 g, 17.5 mmol) in THF (10.0 mL) is added, and the mixture stirred for 2 hours at 0° C. 1N HCl (50.0 mL) is added to the reaction mixture and the aqueous phase extracted with EtOAc (4×40.0 mL). The combined organic phases are dried over MgSO4, filtered and concentrated on the rotovaporator. The product is purified by flash chromatography (CombiFlash), eluting with mixtures of heptanes and EtOAc (0% EtOAc to 40% EtOAc) to yield the desired product (1.76 g, 9.67 mmol, 55%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.92-2.12 (m, 1H) 2.19-2.37 (m, 1H) 2.57-2.69 (m, 2H) 2.71-2.82 (m, 2H) 7.67 (d, J=8.59 Hz, 2H) 7.91 (d, J=8.79 Hz, 2H).

1. stirringthe mixture stirred for 2 hours at 0° C
2. extractionthe aqueous phase extracted with EtOAc (4×40.0 mL)
3. dry with materialThe combined organic phases are dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated on the rotovaporator
6. customThe product is purified by flash chromatography (CombiFlash)
7. washeluting with mixtures of heptanes and EtOAc (0% EtOAc to 40% EtOAc)