反应详情

温度

0 °C

2-(2-Ethoxycarbonylethyl)-3,4-dihydro-5-methoxy-1(2H)-naphthalenone (1.1 g, 4 mmol), from Step 1, was dissolved in 15 mL of dry THF and cooled to 0° C. Diethyl cyanophosphonate (1.18 mL, 8 mmol), commercially available from Aldrich Chemical Company, was added, followed by 8 mL of a 0.5M solution of lithium cyanide (4 mmol) in DMF. The reaction mixture was stirred at ambient temperature overnight and then poured into water. The aqueous mixture was extracted with three portions of diethyl ether/ethyl acetate. The organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in 100 mL of toluene and 1.1 g of p-toluenesulfonic acid was added. The reaction mixture was heated at reflux for 2 h and allowed to cool to ambient temperature. The toluene solution was poured into 5% aqueous sodium bicarbonate and the aqueous mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluted with 10% ethyl acetate in hexane to give 0.8 g (70% yield) of the title compound; MS DCI-NH3 M/Z: 286 (M+H)+, 303 (M+NH4)+.

1. extractionThe aqueous mixture was extracted with three portions of diethyl ether/ethyl acetate
2. washThe organic extracts were washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. dissolutionThe residue was dissolved in 100 mL of toluene
7. addition1.1 g of p-toluenesulfonic acid was added
8. temperatureThe reaction mixture was heated
9. temperatureat reflux for 2 h
10. temperatureto cool to ambient temperature
11. additionThe toluene solution was poured into 5% aqueous sodium bicarbonate
12. extractionthe aqueous mixture was extracted with ethyl acetate
13. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customThe residue was purified by chromatography on silica gel
17. washeluted with 10% ethyl acetate in hexane