反应详情

温度

0 °C

To a 500 mL 3-neck round-bottom flask equipped with an argon inlet and an addition funnel, was added sodium hydride (95%, 1.40 g, 58.3 mmol) followed by tetrahydrofuran (30 mL). The resulting suspension was then cooled to 0° C. and diethyl 2-(2-phenylethyl)malonate (14.0 g, 53.0 mmol) in tetrahydrofuran (20 mL) was added dropwise over 20 minutes. The cooling bath was removed and the reaction mixture was allowed to warm to rt over 45 minutes. A solution of 2-bromo-1-(4-bromophenyl)ethanone (14.72 g, 58.26 mmol) in tetrahydrofuran (40 mL) was rapidly added and the resulting orange-red mixture was stirred at rt for 16 h. The mixture was carefully poured into 300 mL of 1N hydrochloric acid, and the resulting mixture was stirred for 10 minutes and extracted twice with ethyl acetate. The combined extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (Biotage flash 75, 10:90 ethyl acetate/hexane) to afford diethyl 2-[2-(4-bromophenyl)-2-oxoethyl]-2-(2-phenylethyl)malonate (14.8 g, 61%). LC-MS ret. time 3.89 min, m/z 461.2 (MH+); 1H NMR (300 MHz, CDCl3) δ 1.26 (t, 6H), 2.41–2.45 (m, 2H), 2.56–2.59 (m, 2H), 3.67 (s, 2H), 4.23 (q, 4H), 7.14–7.22 (m, 3H), 7.22 (d, 2H), 7.61 (d, 2H), 7.79 (d, 2H).

1. customTo a 500 mL 3-neck round-bottom flask equipped with an argon inlet and an addition funnel
2. customThe cooling bath was removed
3. temperatureto warm to rt over 45 minutes
4. stirringthe resulting mixture was stirred for 10 minutes
5. extractionextracted twice with ethyl acetate
6. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe resulting residue was purified by flash chromatography (Biotage flash 75, 10:90 ethyl acetate/hexane)