反应详情

温度

150 °C

A stirred suspension of anhydrous K2CO3 (79.5 g, 575 mmol) in anhydrous DMF (365 mL) is heated to 150° C. and treated with ethyl 2-cyanopropionate (71.8 g, 564 mmol) via addition funnel over 20 min. The reaction is allowed to cool gradually to ambient temperature over 90 min, and then cooled further (to ca. 12° C.) with a mild ice bath. The yellow reaction mixture is at this point treated with 3,4,5-trifluoronitrobenzene (94.8 g, 535 mmol) via addition funnel over 20 min. The deep purple reaction mixture is stirred overnight at ambient temperature. The deep green reaction mixture is then poured into ice/water (950 mL) and made acidic (from pH 11 to pH 5) with 20% v/v H2SO4/H2O while stirring vigorously and ensuring ample cooling with ice bath. The mixture is then chilled in a refrigerator for 2 h. The amber-brown liquid is extracted with Et2O (1.2 L), taking care to dissolve the large clumps of green-black solid (which accounts for a significant amount of the product). The ethereal layer is washed with H2O (250 mL), saturated aqueous NaHCO3 (2×150 mL), and H2O (2×150 mL), dried over MgSO4, and concentrated under reduced pressure. Trituration (cold hexanes) affords the title compound as a pale tan solid in 77% yield; 1H NMR (400 MHz, CDCl3) δ 7.86 (m, 2H), 4.35 (q, 2H), 2.06 (t, 3H), 1.31 (t, 3H).

1. temperatureto cool gradually to ambient temperature over 90 min
2. temperaturecooled further (to ca. 12° C.) with a mild ice bath
3. stirringwhile stirring vigorously
4. temperatureensuring ample cooling with ice bath
5. temperatureThe mixture is then chilled in a refrigerator for 2 h
6. extractionThe amber-brown liquid is extracted with Et2O (1.2 L)
7. dissolutionto dissolve the large clumps of green-black solid (which
8. washThe ethereal layer is washed with H2O (250 mL), saturated aqueous NaHCO3 (2×150 mL), and H2O (2×150 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated under reduced pressure