Reaction #868

Reaction equation

HCl dioxane

N-t-butoxycarbonyl-DL-isovaline (S)-α-ethylbenzylamide

water

triethylamine

→

α-L-aspartyl-DL-isovaline (S)-α-ethylbenzylamide

Conditions

Workup

1. 1
   ConcentrationThe reaction mixture was concentrated under reduced pressure, 30 ml of ether
2. 2
   workup.ADDITIONwere added to the residue
3. 3
   Concentrationthis was again concentrated
4. 4
   workup.DISSOLUTIONThe residue was dissolved in 20 ml of methylene chloride
5. 5
   TemperatureUnder cooling
6. 6
   workup.STIRRINGthese were stirred for one hour
7. 7
   Temperatureunder cooling
8. 8
   Otherovernight
9. 9
   Otherat room temperature
10. 10
    ConcentrationThe reaction mixture was concentrated under reduced pressure, 50 ml of aqueous 5% citric acid
11. 11
    workup.ADDITIONwere added to the residue, which
12. 12
    Extractionwas extracted two times each with 40 ml of ethyl acetate
13. 13
    Washwashed with 20 ml of water, 25 ml of aqueous 5% sodium hydrogencarbonate and 20 ml of brine, in that order
14. 14
    DryingThe 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 20 ml of methanol
18. 18
    workup.ADDITION0.10 g of 10% Pd-carbon (water content 50%) was added
19. 19
    workup.ADDITION20 ml of water was added to this, the catalyst
20. 20
    Otherwas removed by filtration
21. 21
    Concentrationthe resulting filtrate was concentrated to about 1/5
22. 22
    OtherThis was then stored in a refrigerator overnight
23. 23
    OtherThe crystal thus precipitated
24. 24
    Otherwas removed by filtration
25. 25
    Otherdried

Procedure

10 ml of 4N-HCl/dioxane solution was added to 0.66 (1.97 mmols) of N-t-butoxycarbonyl-DL-isovaline (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 were added to the residue, and this was again concentrated. The residue was dissolved in 20 ml of methylene chloride and 0.24 ml (1.76 mmols) of triethylamine and 0.63 g (1.76 mmols) of β-benzyl N-benzyloxycarbonyl-L-aspartate were added thereto. Under cooling, 0.34 g (1.76 mmols) of water-soluble carbodiimide hydrochloride was 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, 50 ml of aqueous 5% citric acid were added to the residue, which was extracted two times each with 40 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 20 ml of methanol, 0.10 g of 10% Pd-carbon (water content 50%) was added thereto, and the mixture was reduced under hydrogen. 20 ml of water was added to this, the catalyst was removed by filtration, and the resulting filtrate was concentrated to about 1/5. This was then stored in a refrigerator overnight. The crystal thus precipitated was removed by filtration and dried to obtain 0.21 g of α-L-aspartyl-DL-isovaline (S)-α-ethylbenzylamide.

Source