反应详情

温度

15 °C

A 20 L jacketed flask was fit with a gas inlet. A nitrogen purge was begun over the reactor and maintained throughout the process. To the flask was charged 450 g (1.634 mol) of (2R,3R,4S)-3-(2,3-dimethyl-pentanoyl)-4-phenyl-oxazolidin-2-one and 3.375 L tetrahydrofuran. The contents of the reactor were stirred at 15° C. In a separate 3 L round bottom flask, placed in an ice bath, was charged 500 mL of water, 137 g (3.269 mol) of LiOH—H2O and 942 mL (9.81 mol) of 30% wt/wt H2O2. The contents of the 3 L round bottom flask were stirred for 3 minutes and then poured into the 20 L jacketed reactor at a rate such that the temperature did not exceed 25° C. The reaction was stirred at 15° C. for 2 hours and then raised to 25° C. and stirred for an additional 2 hours. The jacket temperature of the reactor was set to −20° C. To the reaction was added 1.66 L of saturated NaHSO3 at a rate such that the temperature of the reaction did not exceed 25° C. The layers were separated. The aqueous layer was extracted 2× with 1 L aliquots of MTBE. The organic phases were combined and concentrated to give a solid/oil mixture. The solid/oil mixture was slurried in 1.7 L of hexane. The slurry was filtered and the collected solids were washed with 1.7 L of hexane. The hexane filtrates were extracted 2× with 1.35 L aliquots of 1N NaOH. The aqueous extracts were combined and extracted with 800 mL of dichloromethane. The aqueous layer was then acidified with 240 mL of concentrated hydrochloric acid. The aqueous solution was extracted 2× with 1 L aliquots of dichloromethane. The organic extracts were combined, dried over MgSO4 and concentrated to give 201 g of the titled compound: 1H-NMR (DMSO) 11.925 (bs, 1H), 2.204-2.135 (m, 1H), 1.556-1.490 (m, 1H), 1.382-1.300 (m, 1H), 1.111-1.000 (m, 1H), 0.952-0.934 (d, 3H, J=7.018), 0.809-0.767 (m, 6H); Gas Chromatogram 9.308 minutes, 98.91% area; Anal Calc'd for C7H14O2: C, 64.58; H, 10.84; N, 0. Found: C, 64.39; H, 10.77; N, 0.18; MS (Ion Mode: APCI) m/z=131 [M+1]+.

1. customwas fit with a gas inlet
2. customA nitrogen purge
3. temperaturemaintained throughout the process
4. customIn a separate 3 L round bottom flask, placed in an ice bath
5. stirringThe contents of the 3 L round bottom flask were stirred for 3 minutes
6. additionpoured into the 20 L
7. customdid not exceed 25° C
8. stirringThe reaction was stirred at 15° C. for 2 hours
9. temperatureraised to 25° C.
10. stirringstirred for an additional 2 hours
11. customwas set to −20° C
12. customdid not exceed 25° C
13. customThe layers were separated
14. extractionThe aqueous layer was extracted 2× with 1 L aliquots of MTBE
15. concentrationconcentrated
16. customto give a solid/oil mixture
17. filtrationThe slurry was filtered
18. washthe collected solids were washed with 1.7 L of hexane
19. extractionThe hexane filtrates were extracted 2× with 1.35 L aliquots of 1N NaOH
20. extractionextracted with 800 mL of dichloromethane
21. extractionThe aqueous solution was extracted 2× with 1 L aliquots of dichloromethane
22. dry with materialdried over MgSO4
23. concentrationconcentrated