反应详情

温度

0 °C

To a 200 mL recovery flask was added (E)-4-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)but-3-en-2-one (30D, 4.81 g, 18.6 mmol, 1.0 eq.), MeOH (100 mL), and dimethylmalonate (30E, 2.13 mL, 18.6 mmol, 1.0 eq.). NaOMe (30% wt in MeOH, 3.66 mL, 19.5 mmol, 1.05 eq.) was added and the reaction mixture was stirred overnight at reflux. LC/MS analysis showed the desired intermediate and the mixture was concentrated and then taken up in 1N aqueous NaOH (100 mL) and refluxed for 1 h. The reaction was then cooled to 0° C. in an ice bath and acidified with 1N HCl until acidic. The reaction mixture was then stirred at 80° C. for 1 h. After cooling to room temperature, EtOAc (200 mL) was added and the organic phase was washed with saturated aqueous NaCl (100 mL). The combined aqueous phases were extracted with EtOAc (100 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to give a foamy brown solid 30F that was taken on to the next step without further purification. (4.9 g, 88%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.67 (m, 3H) 3.79 (s, 3H) 4.54-4.70 (m, 1H) 5.30 (s, 1H) 6.73 (d, J=8.08 Hz, 1H) 7.31 (d, J=7.33 Hz, 1H) 7.39-7.54 (m, 2H) 7.76 (t, J=7.83 Hz, 1H). ESI-MS: m/z 302.3 (M+H)+.

1. temperatureat reflux
2. concentrationthe mixture was concentrated
3. temperaturerefluxed for 1 h
4. stirringThe reaction mixture was then stirred at 80° C. for 1 h
5. temperatureAfter cooling to room temperature
6. additionEtOAc (200 mL) was added
7. washthe organic phase was washed with saturated aqueous NaCl (100 mL)
8. extractionThe combined aqueous phases were extracted with EtOAc (100 mL)
9. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated