تفاعل #81636

معادلة التفاعل

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

المذيبات

Water

Ethyl acetate

ethanol

ethanol

water

ظروف التفاعل

المعالجة

1. 1
   أخرىto obtain a clear solution
2. 2
   درجة الحرارةthe mixture was cooled to about -30° C
3. 3
   درجة الحرارةthe mixture was maintained at about -30° C
4. 4
   درجة الحرارةWith cooling
5. 5
   workup.STIRRINGthe mixture was stirred at about -10° C. for about 2 hours
6. 6
   درجة الحرارةCooling
7. 7
   درجة الحرارةThe mixture was warmed to about 10° C.
8. 8
   أخرىthe phases were separated
9. 9
   غسيلThe organic solution was washed sequentially with aqueous phosphoric acid, aqueous potassium carbonate, and brine
10. 10
    استخلاصThroughout these extractions
11. 11
    استخلاصthe 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
    أخرىwas removed
15. 15
    workup.ADDITIONUnder an inert atmosphere, 10% palladium on carbon (50% water, 0.75 g) was added
16. 16
    أخرىThe 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
    أخرىThe catalyst was removed by filtration
19. 19
    تركيزthe clear filtrate was partially concentrated under vacuum at about 30° C
20. 20
    أخرىa thick precipitate was formed
21. 21
    درجة الحرارةThe suspension was heated
22. 22
    درجة الحرارةto reflux
23. 23
    أخرىto obtain a clear solution
24. 24
    درجة الحرارةThe mixture was cooled to about 0° C.
25. 25
    workup.STIRRINGstirred until crystallization
26. 26
    أخرى(about 1 hour)
27. 27
    أخرىThe product was collected
28. 28
    غسيلthe cake was washed with ethanol
29. 29
    أخرىThe product was dried under vacuum at about 25° C.

الإجراء التجريبي

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.

المصدر