Реакция #45303

Уравнение реакции

(4S)-4-benzyl-1,3-oxazolidin-2-one

BuLi

water

(4S)-4-benzyl-1,3-oxazolidin-2-one

4,4,4-trifluoro-3-methyl-2-butenoic acid chloride

(4S)-4-Benzyl-1,3-oxazolidin-2-one

→

(4S)-4-benzyl-3-[(2E)-4,4,4-trifluoro-3-methyl-but-2-enoyl]-1,3-oxazolidin-2-one

Выход 84.0%

Растворители

EtOH

THF

Условия реакции

Обработка

1. 1
   Другоеat <−40° C
2. 2
   Промывкаwash in with 0.4 L THF
3. 3
   ТемператураThe reaction was warmed to 20-25° C.
4. 4
   workup.ADDITION0.9 L water was added
5. 5
   workup.STIRRINGstirred for 16 h
6. 6
   workup.DISTILLATIONThe THF was distilled off with a bath temperature of 35° C. and vacuum<40 mm Hg
7. 7
   workup.ADDITIONToluene (5.8 L) was added
8. 8
   Другоеthe phases split
9. 9
   Промывкаto wash (2×)
10. 10
    Фильтрацияthe mixture was filtered through Celite
11. 11
    Другоеthe phases split
12. 12
    Промывкаa wash
13. 13
    Фильтрацияthe toluene layer was filtered through Celite
14. 14
    ДругоеThe remaining water was removed
15. 15
    workup.DISTILLATIONThe toluene was distilled off with a bath temperature of 40° C. and vacuum<40 mm Hg
16. 16
    workup.DISTILLATIONAt the end of the distillation the product
17. 17
    Другоеto crystallize with a pot temperature of 30° C
18. 18
    workup.DISTILLATIONDistillation
19. 19
    Другоеis continued to a pot temperature of 35° C.
20. 20
    Другоеgiving a solid mobile mass of 1456 g
21. 21
    workup.STIRRINGWhile stirring at 20-25° C.
22. 22
    Другоеforming crystals
23. 23
    workup.STIRRINGStirring
24. 24
    workup.WAITis continued for 16 h at 15-25° C.
25. 25
    Температураby cooling to 0-5° C.
26. 26
    workup.WAITholding for 1 h
27. 27
    ФильтрацияThe crystals are filtered
28. 28
    Промывкаwashed with filtrate
29. 29
    Другоеdried at 50° C. for 16 h

Методика

(4S)-4-Benzyl-1,3-oxazolidin-2-one (828 g, 4.67 moles) was dissolved in 6.8 L THF and cool to −40 to −50° C. To the solution of (4S)-4-benzyl-1,3-oxazolidin-2-one, 2.5 M BuLi in hexanes (1302 g, 1880 mL, 4.70 mole, 1.01 equivalents) was added while keeping the temperature at <−40° C. To the cold solution of the Li salt of (4S)-4-benzyl-1,3-oxazolidin-2-one, 4,4,4-trifluoro-3-methyl-2-butenoic acid chloride (887 g, 5.14 moles, 1.1 equivalents) was added over 10-30 minutes, all-owing the temperature to rise and wash in with 0.4 L THF. The reaction was warmed to 20-25° C. and stirred for 2 h. 0.9 L water was added and stirred for 16 h. The THF was distilled off with a bath temperature of 35° C. and vacuum<40 mm Hg. Toluene (5.8 L) was added and the phases split. 4-L saturated NaHCO3 was used to wash (2×), the mixture was filtered through Celite and the phases split. 2.5-L water (2×) was used as a wash and the toluene layer was filtered through Celite. The remaining water was removed. The toluene was distilled off with a bath temperature of 40° C. and vacuum<40 mm Hg. At the end of the distillation the product started to crystallize with a pot temperature of 30° C. Distillation is continued to a pot temperature of 35° C. giving a solid mobile mass of 1456 g. The solid is dissolved in 2.9 L (2 vol) EtOH (99.5% EtOH:0.5% toluene). While stirring at 20-25° C., water (1.09 L, 0.75 vol) was added over 1 h forming crystals. Stirring is continued for 16 h at 15-25° C., followed by cooling to 0-5° C. and holding for 1 h. The crystals are filtered, washed with filtrate and dried at 50° C. for 16 h giving 1229 g, 84% of (4S)-4-benzyl-3-[(2E)-4,4,4-trifluoro-3-methyl-but-2-enoyl]-1,3-oxazolidin-2-one.

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