تفاعل #54611

ord-101eefa9a8d24c31a3ac4402adca4457

معادلة التفاعل

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

المتفاعلات

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

الكواشف

لا شيء

المذيبات

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

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىa white solid powder was obtained (44.0 g, mp 179°-184°)
  2. 2
    درجة الحرارةcooled to 0°
  3. 3
    workup.ADDITIONwas added in several portions
  4. 4
    درجة الحرارةmaintaining
  5. 5
    أخرىthe reaction slightly basic
  6. 6
    أخرىThe insoluble matter was removed by filtration
  7. 7
    أخرىthe filtrate evaporated to dryness
  8. 8
    workup.DISSOLUTIONThe oily residue was dissolved in CH2Cl2
  9. 9
    غسيلwashed with 5% HOAc, H2O
  10. 10
    تجفيفdried (Na2SO4)
  11. 11
    أخرىevaporated to a smaller volume (0.5 liter) when
  12. 12
    workup.ADDITIONtreated with petroleum ether
  13. 13
    أخرىThe product crystallized slowly during overnight
  14. 14
    أخرىIt was recrystallized from THF and i-PrOH
  15. 15
    أخرىto yield

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US04148788uspto-grants-1979_04