Triethylamine → TFA Lys-Pro

참여 물질

반응 단계

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)].

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