Verfahren für die Synthese von Perindopril und seiner pharmazeutisch annehmbaren Salzen

摘要

Process for the industrial synthesis of perindopril (I) and its salts, by reaction of benzyl hexahydroindole carboxylic ester (II) with protected amino acid halide (III) in S configuration in the presence of base to form, after removal of the tert. butyloxycarbonyl protecting group, a (S) N-substituted hexahydroindole (IV), and reacting this with ethyl 2-oxopentanoate under pressure of hydrogen in presence of palladium on charcoal to form (I). Process for the industrial synthesis of perindopril (I) and its salts, by reaction of the benzyl hexahydroindole carboxylic ester (II) (Bn = benzyl) with a protected amino acid halide (III) in the S configuration in the presence of a base, to form, after removal of the tert. butyloxycarbonyl protecting group, a (S) N-substituted hexahydroindole (IV), and reacting this with ethyl 2-oxo pentanoate under pressure of hydrogen in the presence of palladium on charcoal to form the compound of formula (I). X = halogen; and BOC = tert. butyloxycarbonyl.