反应详情

温度

0 °C

Charge a flask containing sodium hydride (17.45 g, 0.44 moles) with anhydrous dioxane (500 ml) while cooling at 0° C. Add diethyl malonate (69.88 g, 0.44 moles) dropwise over one hour. Upon reaching ambient temperature, add copper (I) bromide (62.59 g, 0.44 moles). Add 7-bromothieno[3,2-b]pyridine (18.68 g, 87.26 mmol) as a solution in dioxane (50 mL). Heat the reaction to reflux for 18 hours. Concentrate the reaction solution to ˜175 mL. Pour the concentrate into concentrated ammonium hydroxide (2.5 L). Extract the aqueous phase with ethyl acetate (6×300 mL). Wash the organic layers exhaustively with 2 N sodium hydroxide until the blue color dissipates. Treat the organic layers with magnesium sulfate, filter and concentrate. Purification on silica utilizing a solution of 1:1:3 of ether, ethyl acetate and hexane as eluent yields the desired compound (14.6 gm, 57%).

1. additionCharge a flask
2. customUpon reaching ambient temperature
3. temperatureHeat
4. customthe reaction
5. temperatureto reflux for 18 hours
6. concentrationConcentrate the reaction solution to ˜175 mL
7. additionPour the
8. concentrationconcentrate into concentrated ammonium hydroxide (2.5 L)
9. extractionExtract the aqueous phase with ethyl acetate (6×300 mL)
10. washWash the organic layers exhaustively with 2 N sodium hydroxide until the blue color dissipates
11. additionTreat the organic layers with magnesium sulfate
12. filtrationfilter
13. concentrationconcentrate
14. customPurification on silica utilizing a solution of 1:1:3 of ether, ethyl acetate and hexane as eluent