反应详情

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with 106e (366 mg, 0.788 mmol), 106f (194 mg, 0.656 mmol), sodium carbonate (348 mg, 3.28 mmol), DMF (2 mL), water (2 mL) and 1,4-dioxane (10 mL). After bubbling nitrogen through the resulting suspension for 30 min, tetrakis(tri-phenylphosphine)palladium(0) (152 mg, 0.131 mmol) was added. A reflux condenser was attached to the flask, and the reaction mixture was heated at reflux for 16 h. After this time, the mixture was diluted with ethyl acetate (150 mL) and water (100 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was dissolved in THF (2 mL), water (2 mL) and methanol (2 mL). Lithium hydroxide monohydrate (138 mg, 3.28 mmol) was added, and the mixture was stirred at room temperature for 16 h. After this time, the mixture was diluted with ethyl acetate (150 mL) and water (100 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers were washed with brine (100 mL) and dried over sodium sulfate. The drying agent was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography (silica, 90:10 methylene chloride/methanol) to afford 106 in 14% yield (51 mg) as an amorphous off-white solid: mp 145-147° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.20 (s, 1H), 7.89 (s, 1H), 7.55 (d, J=8.5 Hz, 1H), 7.49-7.47 (m, 2H), 7.41 (dd, J=7.0, 2.0 Hz, 1H), 6.87-6.84 (m, 2H), 5.99 (s, 1H), 4.82 (s, 2H), 4.62 (t, J=5.5 Hz, 1H), 4.40 (d, J=5.5 Hz, 2H), 3.96 (t, J=5.5 Hz, 2H), 3.75 (s, 3H), 3.52-3.50 (m, 4H), 2.98 (s, 3H), 2.79 (t, J=5.5 Hz, 2H), 2.35 (s, 3H), 1.09 (t, J=7.0 Hz, 3H); MS (ESI+) m/z 555.3 (M+H).

1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. customAfter bubbling nitrogen through the resulting suspension for 30 min
3. customA reflux condenser was attached to the flask
4. temperaturethe reaction mixture was heated
5. temperatureat reflux for 16 h
6. customthe layers were separated
7. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
8. washthe combined organic layers were washed with brine (100 mL)
9. dry with materialdried over sodium sulfate
10. customThe drying agent was removed by filtration
11. concentrationThe filtrate was concentrated under reduced pressure
12. dissolutionthe resulting residue was dissolved in THF (2 mL)
13. customthe layers were separated
14. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
15. washthe combined organic layers were washed with brine (100 mL)
16. dry with materialdried over sodium sulfate
17. customThe drying agent was removed by filtration
18. concentrationThe filtrate was concentrated under reduced pressure
19. customthe resulting residue was purified by flash column chromatography (silica, 90:10 methylene chloride/methanol)