Reacción #511785

Ecuación de reacción

H-Val-Gly-OBzl.HCl

Z-Glu-OBzl

Boc-Val-Gly-OBzl

HCl dioxane

Triethylamine

HOBt

WSC.HCl

→

Z-Glu(Val-Gly-OBzl)-OBzl

Rendimiento 70.0%

Disolventes

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroDioxane was removed by concentration under reduced pressure, n-hexane (30 ml)
2. 2
   workup.ADDITIONwas added to the residue
3. 3
   Concentraciónthe mixture was concentrated under reduced pressure
4. 4
   Otrowas kept at 0° C
5. 5
   workup.STIRRINGthe mixture was stirred at room temperature for 2 days
6. 6
   ConcentraciónThe reaction mixture was concentrated under reduced pressure
7. 7
   workup.DISSOLUTIONthe residue was dissolved in heated ethyl acetate (1500 ml)
8. 8
   LavadoThe solution was washed with water (200 ml), 5% citric acid aqueous solution (200 ml×twice), saturated brine (150 ml), 5% sodium hydrogencarbonate aqueous solution (200 ml×twice), and saturated brine (150 ml)
9. 9
   SecadoThe organic layer was dried over anhydrous magnesium sulfate
10. 10
    Otrothe magnesium sulfate was removed by filtration
11. 11
    Concentraciónthe filtrate was concentrated under reduced pressure
12. 12
    FiltraciónThe deposited crystals were collected by filtration
13. 13
    Otrodried under reduced pressure

Procedimiento

Boc-Val-Gly-OBzl (5.47 g, 15.0 mmol) was added to 4 N HCl/dioxane solution (40 ml), and the mixture was stirred at room temperature for 50 minutes. Dioxane was removed by concentration under reduced pressure, n-hexane (30 ml) was added to the residue, and the mixture was concentrated under reduced pressure. This procedure was repeated 3 times to quantitatively obtain H-Val-Gly-OBzl.HCl. Then, H-Val-Gly-OBzl.HCl and Z-Glu-OBzl (5.57 g, 15.0 mmol) were dissolved in methylene chloride (50 ml), and the solution was kept at 0° C. Triethylamine (2.30 ml, 16.5 mmol), HOBt (1-hydroxybenzotriazole, 2.53 g, 16.5 mmol), and WSC.HCl (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 3.16 g, 16.5 mmol) were added to the solution, and the mixture was stirred at room temperature for 2 days. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in heated ethyl acetate (1500 ml). The solution was washed with water (200 ml), 5% citric acid aqueous solution (200 ml×twice), saturated brine (150 ml), 5% sodium hydrogencarbonate aqueous solution (200 ml×twice), and saturated brine (150 ml). The organic layer was dried over anhydrous magnesium sulfate, then the magnesium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The deposited crystals were collected by filtration, and dried under reduced pressure to obtain white crystals of Z-Glu(Val-Gly-OBzl)-OBzl (6.51 g, 10.5 mmol).

Fuente