反应详情

A 250-mL oven dried three necked round bottomed flask was equipped with a magnetic stir bar, argon inlet, and temperature probe charged with oven dried powdered molecular sieves 4A° (9.0 g). DCM (30 mL) was added to the flask and the resulting suspension was stirred room temperature for 5 minutes. Diethyl D-tartrate (2.13 g, 10.32 mmol) in DCM (18 mL) was added at room temperature and the mixture was cooled to −30° C. Keeping the temperature at −30° C., titanium (IV) isopropoxide (2.665 mL, 9.03 mmol) was added. The reaction mixture was stirred at −30° C. for 30 minutes followed by 15 minutes at −15° C. The mixture was cooled to −30° C. To this mixture, a solution of compound 16 (4.5 g, 12.9 mmol) in DCM (18 mL) was added. The mixture was stirred for 30 minutes at −30° C. followed by addition of a solution of tert-butyl hydroperoxide (5.0–6.0 M; 9.40 mL, 5.176 mmol). The reaction mixture was stirred between −30° C. to −20° C. for 3 hours to complete the reaction. The reaction was quenched by addition of water (45 mL). The reaction mixture was stirred with vigorous mixing and allowed to warm up to room temperature (15 to 20° C). When the temperature reached ˜15° C., 30% sodium hydroxide solution (10 mL) was added slowly to give a milky white slurry. This slurry was added into a 3.0-L Erlenmeyer flask containing tert-butyl methyl ether (1100 mL). The mixture was stirred for 30 minutes and then filtered on a bed of diatomaceous earth (Celite®). The aqueous layer was separated from the filtrate and discarded. The organic layer was washed with 10% aqueous sodium thiosulfate (100 mL) and water (2×160 mL). The combined organic layer was washed with water (100 mL), brine (50 mL), and dried over magnesium sulfate. The organic layer was concentrated in vacuo to give the title compound in quantitative yield (5.47 g) as an oil.

1. customA 250-mL oven dried three necked round bottomed flask
2. customwas equipped with a magnetic stir bar, argon inlet
3. additiontemperature probe charged with oven
4. customdried
5. additionDCM (30 mL) was added to the flask
6. temperaturethe mixture was cooled to −30° C
7. customat −30° C.
8. stirringThe reaction mixture was stirred at −30° C. for 30 minutes
9. waitfollowed by 15 minutes at −15° C
10. temperatureThe mixture was cooled to −30° C
11. stirringThe mixture was stirred for 30 minutes at −30° C.
12. stirringThe reaction mixture was stirred between −30° C. to −20° C. for 3 hours
13. customthe reaction
14. customThe reaction was quenched by addition of water (45 mL)
15. stirringThe reaction mixture was stirred
16. additionwith vigorous mixing
17. temperatureto warm up to room temperature (15 to 20° C)
18. customreached ˜15° C.
19. addition30% sodium hydroxide solution (10 mL) was added slowly
20. customto give a milky white slurry
21. additionThis slurry was added into a 3.0-L Erlenmeyer flask
22. stirringThe mixture was stirred for 30 minutes
23. filtrationfiltered on a bed of diatomaceous earth (Celite®)
24. customThe aqueous layer was separated from the filtrate
25. washThe organic layer was washed with 10% aqueous sodium thiosulfate (100 mL) and water (2×160 mL)
26. washThe combined organic layer was washed with water (100 mL), brine (50 mL)
27. dry with materialdried over magnesium sulfate
28. concentrationThe organic layer was concentrated in vacuo