Reaktion #81636

Reaktionsgleichung

n-amylamine

Pyridine

Trimethylacetyl chloride

phosphoric acid

1,8-diazabicyclo[5.4.0]undec-7-ene

carbobenzyloxy-L-serine

oxalic acid dihydrate

→

title compound

N-Pentyl-L-Serinamide

Lösungsmittel

Water

Ethyl acetate

ethanol

ethanol

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto obtain a clear solution
2. 2
   Temperaturthe mixture was cooled to about -30° C
3. 3
   Temperaturthe mixture was maintained at about -30° C
4. 4
   TemperaturWith cooling
5. 5
   workup.STIRRINGthe mixture was stirred at about -10° C. for about 2 hours
6. 6
   TemperaturCooling
7. 7
   TemperaturThe mixture was warmed to about 10° C.
8. 8
   Sonstigethe phases were separated
9. 9
   WaschenThe organic solution was washed sequentially with aqueous phosphoric acid, aqueous potassium carbonate, and brine
10. 10
    ExtraktionThroughout these extractions
11. 11
    Extraktionthe aqueous phase was back extracted with ethyl acetate
12. 12
    workup.DISTILLATIONThe combined organic solution was distilled under vacuum at about 25° C. while ethanol
13. 13
    workup.ADDITIONwas added until all of the ethyl acetate
14. 14
    Sonstigewas removed
15. 15
    workup.ADDITIONUnder an inert atmosphere, 10% palladium on carbon (50% water, 0.75 g) was added
16. 16
    SonstigeThe resulting mixture was purged with nitrogen
17. 17
    workup.STIRRINGstirred in the presence of hydrogen at about 25° C. for about 6 hours
18. 18
    SonstigeThe catalyst was removed by filtration
19. 19
    Einengenthe clear filtrate was partially concentrated under vacuum at about 30° C
20. 20
    Sonstigea thick precipitate was formed
21. 21
    TemperaturThe suspension was heated
22. 22
    Temperaturto reflux
23. 23
    Sonstigeto obtain a clear solution
24. 24
    TemperaturThe mixture was cooled to about 0° C.
25. 25
    workup.STIRRINGstirred until crystallization
26. 26
    Sonstige(about 1 hour)
27. 27
    SonstigeThe product was collected
28. 28
    Waschenthe cake was washed with ethanol
29. 29
    SonstigeThe product was dried under vacuum at about 25° C.

Vorschrift

Under an inert atmosphere, 1,8-diazabicyclo[5.4.0]undec-7-ene (5.10 g, 33.5 mmol) was added to a suspension of Part A carbobenzyloxy-L-serine (7.50 g, 31.4 mmol) in ethanol. Ethyl acetate was added and the mixture was agitated (optionally, with heating up to about 50° C.) to obtain a clear solution. Pyridine (0.25 g, 3.2 mmol) was added and the mixture was cooled to about -30° C. Trimethylacetyl chloride (4.12 g, 34.2 mmol) was added and the mixture was maintained at about -30° C. With cooling, n-amylamine (3.00 g, 34.4 mmol) was added and the mixture was stirred at about -10° C. for about 2 hours. Cooling was discontinued and aqueous phosphoric acid was added. The mixture was warmed to about 10° C. and the phases were separated. The organic solution was washed sequentially with aqueous phosphoric acid, aqueous potassium carbonate, and brine. Throughout these extractions, the aqueous phase was back extracted with ethyl acetate. The combined organic solution was distilled under vacuum at about 25° C. while ethanol was added until all of the ethyl acetate was removed. Under an inert atmosphere, 10% palladium on carbon (50% water, 0.75 g) was added. The resulting mixture was purged with nitrogen and then stirred in the presence of hydrogen at about 25° C. for about 6 hours. The catalyst was removed by filtration, and the clear filtrate was partially concentrated under vacuum at about 30° C. The concentrated filtrate was added to a solution of oxalic acid dihydrate (4.35 g, 34.5 mmol) in ethanol and water and a thick precipitate was formed. The suspension was heated to reflux to obtain a clear solution. Water was added at the reflux temperature until a slight turbidity was observed. The mixture was cooled to about 0° C. and stirred until crystallization was complete (about 1 hour). The product was collected and the cake was washed with ethanol. The product was dried under vacuum at about 25° C. to afford the title compound.

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