Reaktion #54611

ord-101eefa9a8d24c31a3ac4402adca4457

Reaktionsgleichung

CCOCC
ether
C[C@@H](OCc1ccccc1)[C@H](NC(=O)[C@@H](N)CC(=O)OCc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)O
H-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Boc-Val-OSu
Cl
HCl
→
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)O)[C@@H](C)OCc1ccccc1
Boc-Val-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH

Edukte

CCOCC
ether
C[C@@H](OCc1ccccc1)[C@H](NC(=O)[C@@H](N)CC(=O)OCc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)O
H-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH
CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Boc-Val-OSu
Cl
HCl

Reagenzien

Keine

Lösungsmittel

CN(C)C=O
DMF
C1CCOC1
THF
C1CCOC1
THF
CCN(CC)CC
Et3N
CCN(CC)CC
Et3N

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Sonstigea white solid powder was obtained (44.0 g, mp 179°-184°)
  2. 2
    Temperaturcooled to 0°
  3. 3
    workup.ADDITIONwas added in several portions
  4. 4
    Temperaturmaintaining
  5. 5
    Sonstigethe reaction slightly basic
  6. 6
    SonstigeThe insoluble matter was removed by filtration
  7. 7
    Sonstigethe filtrate evaporated to dryness
  8. 8
    workup.DISSOLUTIONThe oily residue was dissolved in CH2Cl2
  9. 9
    Waschenwashed with 5% HOAc, H2O
  10. 10
    Trocknendried (Na2SO4)
  11. 11
    Sonstigeevaporated to a smaller volume (0.5 liter) when
  12. 12
    workup.ADDITIONtreated with petroleum ether
  13. 13
    SonstigeThe product crystallized slowly during overnight
  14. 14
    SonstigeIt was recrystallized from THF and i-PrOH
  15. 15
    Sonstigeto yield

Vorschrift

Boc-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH (50.0 g, 46 mmol) was deprotected with HCl (4.15 N) in THF and worked up as usual to give 45.4 g of white solid. It was dissolved in THF (1.5 liters) and treated with ether (7 liters). On standing at 0° overnight a white solid powder was obtained (44.0 g, mp 179°-184°). Part of this material, HCl.H-Asp(OBzl)-Thr(Bzl)-Ser(Bzl)-Ser(Bzl)-Glu(OBzl)-OH (43.7 g, 42.7 mmol) was then dissolved in 500 ml of DMF, cooled to 0°, and treated with Boc-Val-OSu (15.4 g, 49 mmol) and Et3N (10 ml). The mixture was stirred for 15 hours during which time more Et3N (7.9 ml) was added in several portions maintaining the reaction slightly basic. The insoluble matter was removed by filtration and the filtrate evaporated to dryness. The oily residue was dissolved in CH2Cl2, washed with 5% HOAc, H2O, dried (Na2SO4), and evaporated to a smaller volume (0.5 liter) when treated with petroleum ether. The product crystallized slowly during overnight standing. It was recrystallized from THF and i-PrOH to yield, 26.3 g (51.4%); mp 174°-177°; α]D25 =+0.84° (c, 1, THF).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US04148788uspto-grants-1979_04