The objective of the research work is to show a simple method of synthesis of 4-cyclohexyl-S-proline as an intermediate product in the preparation of Fosinopril - prodrug used in the treatment of hypertension and acute or chronic congestive heart failure.

Our three-steps method includes simple, commonly known reactions such as aldol reaction, Michael reaction, hydrogen reduction.

In the first stage of the suggested synthesis we used aldol condensation. That powerful method is used to form carbon–carbon bonds between clohexane carboxaldehyde condensed with molecule containing an acidic hydrogen atom.

In the second step of the 4-cyclohexyl-S-proline synthesis the Michael reaction was used. In which consist of the nucleophilic addition of a carboanion to an α, β unsaturated carbonyl compound and formation of C-C bonds. The resulting product contains one asymmetric carbon atom. In an extension of those studies, we report amplification of our qualitative reports by determining the enantiomeric excess after second and third step of reaction.

In the synthesis the Phase Transfer Catalysis (PTC) method was applied. Moreover, the reaction was carried out with the primary and secondary amines as catalyst. The final product was collected and purified by repeated column chromatography on silica gel. The structures were confirmed by spectroscopic methods: UV-vis, IR, ¹H NMR.

The presented method of preparation of 4-cyclohexyl-S-proline, as an intermediate in the synthesis of Fosinopril, is highly effective and competitive with other methods presented in the literature.

That work is a part of a research project No. N N209 237336 financed by the Ministry of Science and Higher Education.

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