4-Methylmorpholine → Z-Gly-Leu-PheCH2F

HRID 2373071

Reaktionsgleichung

Reaktionsgleichung von HRID 2373071
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[CH2:7][CH:8]([CH3:10])[CH3:9])=[O:4].N(C(OCC1C=CC=CC=1)=O)CC(O)=O.[OH-].[Na+].CN1CCOCC1.[NH2:48][C@H:49]([C:57]([CH2:59][F:60])=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.Cl>C1COCC1.CN(C=O)C>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:2][C:3]([NH:5][C@H:6]([C:11]([NH:48][C@H:49]([C:57]([CH2:59][F:60])=[O:58])[CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:13])[CH2:7][CH:8]([CH3:9])[CH3:10])=[O:4]

Komponenten

8

Edukt 5

HCID 79724-Methylmorpholine2×HCID 14349BenzyloxycarbonylglycineHCID 14798Sodium HydroxideHCID 96816Z-Gly-Leu-OH2×HCID 131717227PheCH2F hydrochloride

Produkt 1

HCID 131717229Z-Gly-Leu-PheCH2FAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Z-Gly-LeuOH was made by mixed anhydride coupling of Z-GlyOH and LeuOBzl tosylate, followed by NaOH hydrolysis of the benzyl ester. To a solution of Z-Gly-LeuOH (0.223 g, 0.69 mmol) in THF (4 mL) at -20° C. was added NMM (76 uL, 0.69 mmol), followed by IBCF (90 uL, 0.69 mmol). After 10 minutes, a precooled solution of PheCH2F hydrochloride (0.15 g, 0.69 mmol) in DMF (1 mL) was added, followed by a second equivalent (76 uL, 0.69 mmol) of NMM. After 30 minutes of stirring, the mixture was quenched with 1M HCl (5 mL), extracted with ethyl acetate (20 mL), washed with saturated aqueous NaHCO3 (6 mL), brine (5 mL), dried over MgSO4, filtered, and evaporated to dryness. The residue was crystallized from ether/hexane to give 0.18 g (54%) of Z-Gly-Leu-PheCH2F.

Aufarbeitung

  1. customthe mixture was quenched with 1M HCl (5 mL)
  2. extractionextracted with ethyl acetate (20 mL)
  3. washwashed with saturated aqueous NaHCO3 (6 mL), brine (5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe residue was crystallized from ether/hexane

Quellen und Nachweise

ORD-Eintrag
ord-1a2cdad7a44c445db5cfed2e12ca1dee
Quelldatensatz
uspto-grants-1992_03
Patentnummer
US05101068

Verknüpfte Notizen

Wird geladen…