反应详情

温度

23 °C

The compound of Step A of Example 1 (31.0 g, 0.13 mol) and iodobenzene (40.2 g, 0.19 mol) were suspended in sulfuric acid (100 mL) and stirred for 3 days at 23° C. The mixture was poured onto ice and extracted with dichloromethane (200 mL). The dichloromethane layer was dried over magnesium sulfate and evaporated under reduced pressure. Methanol (200 mL) and thionyl chloride (6 mL) were added and the mixture and heated at reflux for 30 min. The methanol was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (200 mL). Lithium borohydride (55 mL, 2N in tetrahydrofuran, 0.11 mol) was added slowly and after completion of the addition, the mixture was heated at reflux for 1 h. The mixture was cooled, and quenched by slow addition of aqueous hydrochloric acid (200 mL, 1N). The mixture was extracted with dichloromethane (200 mL), dried over magnesium sulfate and evaporated under reduced pressure. The residue was then treated with toluene (100 mL) and thionyl chloride (23 mL, 0.3 mol). The mixture was heated to reflux for 45 min and then evaporated under reduced pressure. The residue was dissolved in methanol (200 mL) and treated with aqueous sodium hydroxide (30 mL, 50% solution). The mixture was heated to reflux for 30 min and then evaporated under reduced pressure. The residue was partitioned between water (100 mL) and dichloromethane (200 mL). The dichloromethane solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel using hexanes/ethyl acetate (10:1) as eluent to give the title compound (23.1 g) as a white solid: m.p.: 105°-106° C. 1H NMR (CDCl3, 200 MHz) δ 7.7 (m,2H), 7.5 (m, 1H), 7.1 (m, 1H), 7.0 (m,2H), 5.4 (m, 1H), 4.8 (m, 1H), 4.3 (m, 1H).

1. additionThe mixture was poured onto ice
2. extractionextracted with dichloromethane (200 mL)
3. dry with materialThe dichloromethane layer was dried over magnesium sulfate
4. customevaporated under reduced pressure
5. additionMethanol (200 mL) and thionyl chloride (6 mL) were added
6. temperaturethe mixture and heated
7. temperatureat reflux for 30 min
8. customThe methanol was removed under reduced pressure
9. dissolutionthe residue was dissolved in tetrahydrofuran (200 mL)
10. additionafter completion of the addition
11. temperaturethe mixture was heated
12. temperatureat reflux for 1 h
13. temperatureThe mixture was cooled
14. customquenched by slow addition of aqueous hydrochloric acid (200 mL, 1N)
15. extractionThe mixture was extracted with dichloromethane (200 mL)
16. dry with materialdried over magnesium sulfate
17. customevaporated under reduced pressure
18. temperatureThe mixture was heated
19. temperatureto reflux for 45 min
20. customevaporated under reduced pressure
21. dissolutionThe residue was dissolved in methanol (200 mL)
22. additiontreated with aqueous sodium hydroxide (30 mL, 50% solution)
23. temperatureThe mixture was heated
24. temperatureto reflux for 30 min
25. customevaporated under reduced pressure
26. customThe residue was partitioned between water (100 mL) and dichloromethane (200 mL)
27. dry with materialThe dichloromethane solution was dried over magnesium sulfate
28. customevaporated under reduced pressure