反应详情

In a 3-neck round bottom flask, fitted with an internal thermometer and addition funnel, a mixture of sodium hydride (60% in mineral oil, 4.14 g) in THF (200 mL), under argon, was cooled to 10° C. (Diethoxyphosphoryl)acetic acid ethyl ester (21 mL) was added dropwise (heat and gas evolution), keeping the internal temperature below room temperature. After addition, the reaction mixture was stirred at room temperature for minutes, and then cooled to 0° C. A solution of 2-methoxyphenyl acetone (5 g) in THF (25 mL) was added dropwise over 5 minutes. The reaction was allowed to warm to room temperature overnight. With active cooling, the reaction was quenched with H2O (200 mL), then AcOH (to pH ˜6) and extracted with EtOAc. The combined organics were washed with NaHCO3, water, and brine, dried over Na2SO4, and concentrated. The crude residue was purified by flash column chromatography to give the desired compound (5.73 g). 1H-NMR: 400 MHz, (CDCl3) δ: 7.24 (app dt, 1H), 7.10 (dd, 1H), 6.92 (d, 1H), 6.88 (d, 1H), 5.58 (s, 1H), 4.13 (q, 2H), 3.82 (s, 3H), 3.46 (s, 2H), 1.26 (t, 3H).

1. customIn a 3-neck round bottom flask, fitted with an internal thermometer and addition funnel
2. additionwas added dropwise
3. temperature(heat and gas evolution)
4. customthe internal temperature below room temperature
5. additionAfter addition
6. temperaturecooled to 0° C
7. temperatureto warm to room temperature overnight
8. customWith active cooling, the reaction was quenched with H2O (200 mL)
9. extractionAcOH (to pH ˜6) and extracted with EtOAc
10. washThe combined organics were washed with NaHCO3, water, and brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customThe crude residue was purified by flash column chromatography