반응 #45303

반응 방정식

(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

수율 84.0%

용매

EtOH

THF

반응 조건

후처리

1. 1
   기타at <−40° C
2. 2
   세척wash in with 0.4 L THF
3. 3
   온도The 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
   기타the phases split
9. 9
   세척to wash (2×)
10. 10
    여과the mixture was filtered through Celite
11. 11
    기타the phases split
12. 12
    세척a wash
13. 13
    여과the toluene layer was filtered through Celite
14. 14
    기타The 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
    기타to crystallize with a pot temperature of 30° C
18. 18
    workup.DISTILLATIONDistillation
19. 19
    기타is continued to a pot temperature of 35° C.
20. 20
    기타giving a solid mobile mass of 1456 g
21. 21
    workup.STIRRINGWhile stirring at 20-25° C.
22. 22
    기타forming crystals
23. 23
    workup.STIRRINGStirring
24. 24
    workup.WAITis continued for 16 h at 15-25° C.
25. 25
    온도by cooling to 0-5° C.
26. 26
    workup.WAITholding for 1 h
27. 27
    여과The crystals are filtered
28. 28
    세척washed with filtrate
29. 29
    기타dried at 50° C. for 16 h

실험 절차

(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.

출처