Degussa Aktiengesellschaft

Degussa Aktiengellschaft

Klaus Stingl

Karlheinz Drauz

Matthias Kottenhahn

Roland Moller

Michael Kraft

Thomas Tacke

Horst Bethge

Herbert Tanner

Claus Rehren

Gerhard Sator

Roland M&ouml;ller

A method of isolating 1-&lsqb;N -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetyl&rsqb;-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE). The solvent or solvent mixture used for the extraction is also a main constituent of the solvent or solvent mixture from which the crystallization takes place. High yield as well as good purity of the end product are obtained, without distillation. 1-&lsqb;N -((S)-ethoxycarbonyl)-3-phenylpropyl)-N -trifluoroacetyl&rsqb;-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE) is described as a precursor for producing an ACE inhibitor.

1-&lsqb;N2-((S)-ethoxycarbonyl)-3-phenylproply)-N6-trifluoroacetyl&rsqb;-L-ysyl-L-proline (lisinopril (TFA) ethyl ester, LPE)

Process for the continuous production of basic cyclic optically active

There is provided a process for the work-up of this material having the formula ##STR1## because of its poor crystallizability has heretofore been available only with large yield losses. The yield losses are due to the fact that the crystals of this compound are associated with large amounts of residual solvent material which gives rise to complex and expensive drying procedures. In accordance with the present invention the crude LPE is dried by means of fluid or supercritical carbon dioxide which maces it possible to reduce drying times from the previous range of about 124 hours to about 10 hours for the same amount of product and thus produce a dry LPE which has smaller amounts of residual solvent, as well as smaller by-products than that obtained by conventional drying.

Process for the preparation of 1-(N 2-(S)-ethoxycarbonyl)--3

Process for the production .beta.-amino-.alpha.-hydroxycarboxylic acids

A method of isolating 1-�N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE). The solvent or solvent mixture used for the extraction is also a main constituent of the solvent or solvent mixture from which the crystallization takes place. High yield as well as good purity of the end product are obtained, without distillation. 1-�N.sup.2 -((S)-ethoxycarbonyl)-3-phenylpropyl)-N.sup.6 -trifluoroacetyl!-L-lysyl-L-proline (lisinopril (TFA) ethyl ester, LPE) is described as a precursor for producing an ACE inhibitor.

Method of isolating 1-�N.sup.2

Method for the preparation of N-protected 4-ketoproline derivatives of formula I ##STR1## by oxidation of the corresponding N-protected 4-hydroxyproline derivatives of ##STR2## using the system TEMPO (2,2,6,6-tetramethylpiperidinyl oxy free radical)/NaOCl.

Method for the preparation of N-substituted 4-ketoproline derivatives

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Alzenau, Germany

Klaus Stingl