Reacción #72431

Ecuación de reacción

HOBt

triethylamine

H2O

WSC.HCl

Z-Glu-OBzl

H-Nle-OBzl.HCl

→

Z-Glu(Nle-OBzl)-OBzl

Disolventes

methylene chloride

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe resulting reaction solution
2. 2
   TemperaturaThe temperature of the reaction solution was gradually raised
3. 3
   ConcentraciónThen, the reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL)
4. 4
   workup.ADDITIONwas added to the resulting residue
5. 5
   Lavadothe organic phase was then washed once with water (30 mL), twice with a 5% aqueous solution of citric acid (30 mL), once with a saturated common salt solution (30 mL), twice with a 5% aqueous solution of sodium hydrogen carbonate (30 mL) and once with a saturated common salt solution (30 mL)
6. 6
   SecadoThen, the organic phase was dried over anhydrous magnesium sulfate
7. 7
   OtroThe magnesium sulfate was removed through filtration
8. 8
   Concentraciónthe filtrate was concentrated under reduced pressure
9. 9
   OtroThe resulting residue was recrystallized from ethyl acetate and n-hexane
10. 10
    Otrothe crystals thus obtained
11. 11
    Filtraciónwere collected through filtration
12. 12
    Otrodried under reduced pressure

Procedimiento

The resulting H-Nle-OBzl.HCl was dissolved in methylene chloride (30 mL) and the resulting reaction solution was maintained at 0° C. To the reaction solution, Z-Glu-OBzl (N-α-carbobenzoxy-L-glutamic acid α-benzyl ester, 0.70 g, 1.90 mM), triethylamine (0.29 mL, 1.1 eq., 2.10 mM), HOBt.H2O (1-hydroxybenzotriazole hydrate, 0.32 g, 1.1 eq., 2.10 mM), and WSC.HCl (0.41 g, 1.1 eq., 2.10 mM) was added. The temperature of the reaction solution was gradually raised and stirred at room temperature overnight (16 hours). Then, the reaction mixture was concentrated under reduced pressure, ethyl acetate (100 mL) was added to the resulting residue, and the organic phase was then washed once with water (30 mL), twice with a 5% aqueous solution of citric acid (30 mL), once with a saturated common salt solution (30 mL), twice with a 5% aqueous solution of sodium hydrogen carbonate (30 mL) and once with a saturated common salt solution (30 mL). Then, the organic phase was dried over anhydrous magnesium sulfate. The magnesium sulfate was removed through filtration and the filtrate was concentrated under reduced pressure. The resulting residue was recrystallized from ethyl acetate and n-hexane, the crystals thus obtained were collected through filtration and dried under reduced pressure to give crystals of Z-Glu(Nle-OBzl)-OBzl (0.91 g).

Fuente