N-Alkylation of 2-oxo-4-phenylbutanoate acid
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 10, October, 2020
1927
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compound condensation with the formation of azomethine
(i.e., accelerates the attainment of equilibrium). At the
same time, the hydrogenation of the azomethine bond of
the formed Schiff base proceeds on active metal nano-
particles. Hydrogenation of the azomethine bond with the
conversion of the compound into the target product, in
turn, also contributes to the formation of the intermediate
condensation product, azomethine, especially since the
hydrogenation step, in contrast to the condensation, is
a non-equilibrium process. Thus, the high yield of the
target product is achieved due to both the acceleration of
the process of condensation of amine with carbonyl com-
pound and the non-equilibrium step of hydrogenation of
the azomethine bond in the intermediate product. Con-
cerning selectivity and activity in the one-step synthesis
of enalapril by reductive N-alkylation of dipeptide
α-alanyl-α-proline with ethyl 2-oxo-4-phenylbutanoate,
palladium-containing catalysts are superior to nickel-
containing metal-polymer and heterogeneous analogs.
In conclusion, nickel- or palladium-containing poly-
mers turned out to be efficient in the catalytic synthesis of
the drug 1-[N-((S)-1-carboxy-3-phenylpropyl)-α-alanyl]-
α-proline-1´-ethyl ether, or enalapril, under mild condi-
tions of the process. The highest selectivity is displayed by
palladium catalysts based on industrial anion exchangers;
therefore, these contacts can become the basis for the
development of efficient methods for obtaining medicinal
organic substances.
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Received September 24, 2018;
in revised form December 24, 2019;
accepted March 27, 2020
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