反应详情

Zinc/copper couple was freshly prepared by quickly washing zinc dust with 1N HCl (4×100 mL) in a flask and decanting the supernatant. The solid was then washed in the same manner with distilled water (4×120 mL), 2 mol % CuSO4 solution (2×200 mL), distilled water (4×120 mL), EtOH (4×120 mL) and Et2O (5×100 mL). The Et2O washes were poured onto a funnel and dried by vacuum filtration. The resulting solid was added to a 3 L flask and dried under vacuum at 50° C. for 30 min, then cooled to RT. The flask was fitted with an addition funnel and reflux condenser, then purged with nitrogen and kept under N2 throughout the reaction. Next, 650 mL of Et2O was added followed by I2 (0.886 g, 3.49 mmol), and the solution was stirred and heated to reflux. Once at reflux, heating was stopped and diiodomethane (150 mL, 1865 mmol) was slowly added making sure to not allow the reaction to reflux out of control. (2R,3R)-7-methyl-2,3-diphenyl-1,4-dioxaspiro[4.5]dec-6-ene (214 g, 698 mmol in 600 mL Et2O) was then added to the reaction mixture, followed by an additional 0.5 eq of diiodomethane. The reaction was heated to reflux, and the reaction was monitored by LCMS. After 1.5 h the reaction was cooled to RT and quenched with saturated aq Na2CO3 (170 g in 800 mL water). The mixture was stirred for 30 min, then filtered through celite. The inorganics were washed with Et2O (2 L), then the combined organics were washed with saturated NH4Cl (1 L), saturated NaHCO3 (1 L), brine (1 L), then dried over MgSO4, filtered and concentrated to afford the crude product. Methanol (350 mL) was added to the residue and the suspension was heated to 50° C. The resultant solution was cooled with stirring to RT to crystallize the product. The slurry was stirred overnight at RT, then cooled to 0° C., and stirred for an additional 1 h. The slurry was filtered, washed with a minimal amount of MeOH and dried under reduced pressure to afford the desired product as a white solid (137 g, 61% yield).

1. customdecanting the supernatant
2. washThe solid was then washed in the same manner with distilled water (4×120 mL), 2 mol % CuSO4 solution (2×200 mL)
3. distillationdistilled water (4×120 mL), EtOH (4×120 mL) and Et2O (5×100 mL)
4. additionThe Et2O washes were poured onto a funnel
5. customdried by vacuum filtration
6. additionThe resulting solid was added to a 3 L flask
7. customdried under vacuum at 50° C. for 30 min
8. customThe flask was fitted with an addition funnel
9. temperaturereflux condenser
10. custompurged with nitrogen
11. customkept under N2 throughout the reaction
12. temperatureheated to reflux
13. temperatureOnce at reflux
14. temperatureheating
15. customthe reaction
16. temperatureto reflux out of control
17. temperatureThe reaction was heated
18. temperatureto reflux
19. temperatureAfter 1.5 h the reaction was cooled to RT
20. customquenched with saturated aq Na2CO3 (170 g in 800 mL water)
21. stirringThe mixture was stirred for 30 min
22. filtrationfiltered through celite
23. washThe inorganics were washed with Et2O (2 L)
24. washthe combined organics were washed with saturated NH4Cl (1 L), saturated NaHCO3 (1 L), brine (1 L)
25. dry with materialdried over MgSO4
26. filtrationfiltered
27. concentrationconcentrated
28. customto afford the crude product
29. temperaturethe suspension was heated to 50° C
30. stirringwith stirring to RT
31. customto crystallize the product
32. stirringThe slurry was stirred overnight at RT
33. temperaturecooled to 0° C.
34. stirringstirred for an additional 1 h
35. filtrationThe slurry was filtered
36. washwashed with a minimal amount of MeOH
37. customdried under reduced pressure