Réaction #867

Équation de réaction

water

HOBt

HCl dioxane

N-t-butoxycarbonyl-α,α-diethylglycine (S)-α-ethylbenzylamide

triethylamine

β-benzyl-N-benzyloxycarbonyl-L-aspartate

→

α-L-aspartyl-α,α-diethylglycine (S)-α-ethylbenzylamide

Rendement 29.3%

Conditions de réaction

Traitement

1. 1
   ConcentrationThe reaction mixture was concentrated under reduced pressure, 30 ml of ether
2. 2
   workup.ADDITIONwas added to the residue
3. 3
   Concentrationthis was again concentrated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in 25 ml of methylene chloride
5. 5
   TempératureUnder cooling
6. 6
   workup.STIRRINGthese were stirred for one hour
7. 7
   Températureunder cooling
8. 8
   Autreovernight
9. 9
   Autreat room temperature
10. 10
    ConcentrationThe reaction mixture was concentrated under reduced pressure and 50 ml of aqueous 5% citric acid
11. 11
    workup.ADDITIONwere added
12. 12
    ExtractionThe resulting residue was extracted two times each with 50 ml of ethyl acetate
13. 13
    Lavagewashed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order
14. 14
    SéchageThe resulting organic layer was dried with anhydrous magnesium sulfate
15. 15
    Filtrationfiltered
16. 16
    Concentrationthe resulting filtrate was concentrated under reduced pressure
17. 17
    workup.DISSOLUTIONThe residue was dissolved in 30 ml of methanol
18. 18
    workup.ADDITION0.30 g of 10% Pd-carbon (water content 50) was added
19. 19
    workup.ADDITION40 ml of water was added to this, the catalyst
20. 20
    Autrewas removed by filtration
21. 21
    Concentrationthe resulting filtrate was concentrated to about 1/4
22. 22
    AutreThis was then stored in a refrigerator overnight
23. 23
    AutreThe crystal thus precipitated
24. 24
    Autrewas removed by filtration
25. 25
    Autredried

Mode opératoire

19 ml of 4N-HCl/dioxane solution were added to 1.31 g (3.76 mmols) of N-t-butoxycarbonyl-α,α-diethylglycine (S)-α-ethylbenzylamide, and the mixture was stirred at room temperature for one hour. The reaction mixture was concentrated under reduced pressure, 30 ml of ether was added to the residue, and this was again concentrated. The residue was dissolved in 25 ml of methylene chloride, and 0.55 ml (4.13 mmols) of triethylamine and 1.48 g (4.13 mmols) of β-benzyl-N-benzyloxycarbonyl-L-aspartate were added thereto. Under cooling, 0.79 g (4.13 mmols) of water-soluble carbodiimide hydrochloride and 0.51 g (3.76 mmols) of HOBt were added thereto, and these were stirred for one hour under cooling and then overnight at room temperature. The reaction mixture was concentrated under reduced pressure and 50 ml of aqueous 5% citric acid were added. The resulting residue was extracted two times each with 50 ml of ethyl acetate and then washed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order. The resulting organic layer was dried with anhydrous magnesium sulfate and filtered, and the resulting filtrate was concentrated under reduced pressure. The residue was dissolved in 30 ml of methanol, 0.30 g of 10% Pd-carbon (water content 50) was added thereto, and the mixture was reduced under hydrogen. 40 ml of water was added to this, the catalyst was removed by filtration, and the resulting filtrate was concentrated to about 1/4. This was then stored in a refrigerator overnight. The crystal thus precipitated was removed by filtration and dried to obtain 0.40 g (1.10 mmols) of α-L-aspartyl-α,α-diethylglycine (S)-α-ethylbenzylamide.

Source