Triethylamine → TFA Lys-Pro

HRID 273896

Reaktionsgleichung

Reaktionsgleichung von HRID 273896
[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[NH2:8][C@H:9]([C:15]([N:17]1[CH2:24][CH2:23][CH2:22][C@H:18]1[C:19]([OH:21])=[O:20])=[O:16])[CH2:10][CH2:11][CH2:12][CH2:13][NH2:14].C(OC(=O)C(=O)CCC1C=CC=CC=1)C.C(N(CC)CC)C.[H][H]>C(O)CCC.[Ni]>[C:1]([OH:7])([C:3]([F:6])([F:5])[F:4])=[O:2].[CH2:23]1[CH2:24][N:17]([C:15]([C@@H:9]([NH2:8])[CH2:10][CH2:11][CH2:12][CH2:13][NH2:14])=[O:16])[C@@H:18]([C:19]([OH:21])=[O:20])[CH2:22]1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 562087Ethyl alpha-oxobenzenebutanoate2×HCID 131718847TFA Lys-Pro-OHHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 131718846TFA Lys-Pro

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 935NickelKatalysatorHCID 2631-ButanolLösungsmittel

Versuchsvorschrift

150 mmoles H-Nε -TFA-Lys-Pro-OH (50.9 g) were taken up in 120 ml n-butanol and approximately 50 ml n-butanol distilled off under vacuum. The solution was diluted with 500 ml ethanol. 22.5 g molecular sieve 3 A, 34 g 2-oxo-4-phenyl butyric acid ethyl ester and 30 mmoles triethylamine (4.2 ml) are added and the mixture agitated 2 hours under anhydrous conditions. Three teaspoons dehydrated Raney nickel were now added and the mixture was agitated for 4 hours at under an atmosphere of 4 bars of H2. After this time, the pressure was released, another 12.4 g 2-oxo-4-phenyl butyric acid ethyl ester was added and the mixture was reagitated for 2 hours. Then a pressure of 4 bars of hydrogen was applied and the mixture was hydrogenated a further 4 hours at this pressure. The catalyst was separated off (it can be directly reused) and the solution was evaporated to a small volume. Conversion (according to HPLC) relative to Nε -TFA-Lys-Pro: approximately 95%, product yield (according to HPLC): 90%, diastereomer ratio: SSS:RSS-isomer=95.5. The residue was suspended in 450 ml water and 450 ml 1,1,1-trichloroethane at 5° C., the pH was adjusted to 9.6 in the aqueous phase with 50% NaOH and the phases were thoroughly mixed. The organic phase was separated off and the aqueous product phase was post-extracted with 100 ml 1,1,1-trichloroethane. The pH of 4.6 was now adjusted to 5 in the aqueous phase and this phase was extracted twice with 400 ml 1,1,1-trichloroethane. The organic phase was evaporated to low volume and taken up in 250 ml methyl-tert.butyl ether. The solution was cooled down to 0° C. and seeded. Yield: 48 g (60% of theory), SSS diastereomer content: >99%, [α]D20 :-25.5° [(c=1 in MeOH/ ·1N HCl (1:1)].

Aufarbeitung

  1. distillationapproximately 50 ml n-butanol distilled off under vacuum
  2. additionThe solution was diluted with 500 ml ethanol
  3. additionwere now added
  4. stirringthe mixture was agitated for 4 hours at under an atmosphere of 4 bars of H2
  5. waitthe mixture was reagitated for 2 hours
  6. waitthe mixture was hydrogenated a further 4 hours at this pressure
  7. customThe catalyst was separated off (it
  8. customwas evaporated to a small volume

Quellen und Nachweise

ORD-Eintrag
ord-2c0099b609b34e829469ee8b21511635
Quelldatensatz
uspto-grants-1995_02
Patentnummer
US05387696

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