Ethyl Acetate → Boc-Ser(Bzl)-Gly-OCH3

Temperatur

0 °C

Dipeptide Boc-Ser(Bzl)-Gly-OH: A solution of Boc-Ser(Bzl)-OH (23.6 g) and N-hydroxysuccinimide (9.8 g) in EtOAc (400 mL) was cooled to 0° C. A solution of DCC (71.54 g) in EtOAc (100 mL) was added to the cooled solution. The mixture was stirred at 0° C. for 4 h and then filtered. The collected solid was washed with EtOAc. The filtrate was cooled to 0° C. HCl.H-Gly-OCH3 (10.67 g) and DIEA (42 mL) was added to the cooled solution. The mixture was stirred for 18 h while the temperature of the mixture gradually came to room temperature. The mixture was filtered. The filtrate was concentrated to ca 400 mL, washed serially with H2O, 5% aqueous NaHCO3, 1N HCl and H2O, dried (Na2SO4 /MgSO4), and concentrated to dryness. The residual oil was dissolved in Et2O (100 mL). A flocculent precipitate developed which was removed by filtration. The filtrate was concentrated to dryness and dried under reduced pressure to give Boc-Ser(Bzl)-Gly-OCH3 as a colorless oil (28.7 g). A solution of the latter compound (28.0 g) in dioxane (140 mL) and H2O (60 mL) was cooled to 0° C. A solution of NaOH (4.0 g) in H2O (80 mL) was added dropwise to preceding solution. The mixture was stirred at 0° C. during the addition and for 15 min thereafter. The mixture was diluted with H2O and washed with Et 2 O. The aqueous phase was separated and shaken with EtOAc. Solid citric acid was added to mixture (pH=3-4). The aqueous layer was separated from the EtOAc and extracted with fresh EtOAc. The combined organic extracts were washed with H2O, dried (Na2SO4) and concentrated. The glassy residue was dried under high vacuum to give the dipeptide Boc-Ser(Bzl)-Gly-OH (27.22 g).

1. filtrationfiltered
2. washThe collected solid was washed with EtOAc
3. temperatureThe filtrate was cooled to 0° C
4. additionH-Gly-OCH3 (10.67 g) and DIEA (42 mL) was added to the cooled solution
5. stirringThe mixture was stirred for 18 h while the temperature of the mixture
6. customgradually came to room temperature
7. filtrationThe mixture was filtered
8. concentrationThe filtrate was concentrated to ca 400 mL
9. washwashed serially with H2O, 5% aqueous NaHCO3, 1N HCl and H2O
10. dry with materialdried (Na2SO4 /MgSO4)
11. concentrationconcentrated to dryness
12. dissolutionThe residual oil was dissolved in Et2O (100 mL)
13. customwas removed by filtration
14. concentrationThe filtrate was concentrated to dryness
15. customdried under reduced pressure

ORD-Eintrag

ord-f8a1fe95a3e64a2fb26fd7ca8db521ac

Quelldatensatz

uspto-grants-1990_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US04891358