反应详情

温度

2.5 °C

To a mixture of NaH (16.6 g, 657 mmol, dry) in THF (150 mL) was added dropwise over 30 min with stirring at 0-5° C. a solution of diethyl malonate (104.7 g, 654 mmol) in THF (120 mL). To this translucent mixture was then immediately added a solution of 2,3,4-trifluorobenzonitrile (47.7 g, 304 mmol) in THF (50 mL) dropwise with stirring at 0-5° C. The ice bath was then removed and the mixture allowed to stir at room temperature for 4 days. The clear yellow reaction was then diluted with 1 M HCl (350 mL), 4 N HCl was added to pH ˜2 (paper), and the mixture was extracted with 1:1 ether/hexanes (1×350 mL, 1×200 mL). The combined organic layers were washed with brine (1×300 mL), dried (Na2SO4), and concentrated to afford the title compound (88.1 g, 98%) as a 1.35:1 mixture of regioisomers. 1H NMR of major (desired) regioisomer (300 MHz, CDCl3) δ 7.51 (ddd, J=8.7 Hz, 4.6 Hz, 1.8 Hz, 1H), 7.29 (dt, J=8.9 Hz, 7.2 Hz, 1H), 5.12 (s, 1H), 4.35-4.20 (m, 4H), 1.31 (t, 7.2 J=Hz, 6H).

1. additionwas added dropwise over 30 min
2. customThe ice bath was then removed
3. stirringto stir at room temperature for 4 days
4. customThe clear yellow reaction
5. additionwas added to pH ˜2 (paper)
6. extractionthe mixture was extracted with 1:1 ether/hexanes (1×350 mL, 1×200 mL)
7. washThe combined organic layers were washed with brine (1×300 mL)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated