AN IMPROVED PROCESS FOR THE PREPERATION OF LISNOPRIL USEFUL AS ANGIOTENSIN-CONVERTING ENZYME INHIBITORS A NOVEL INTERMEDIATE FOR THE PREPERATION OF LISINOPRIL AND A PROCESS FOR ITS PREPERATION

摘要

: This application disclose an improved process for the preparation of Lisinopril dihydrate, (S)-1-(N2_1 (1-carboxy-3-phenyl proply)-L-Lysyll-L-proline dihydrate of the formula I Which comprises, (i) Protecting the N6-position of L-Lysine with trifluoro acetyl group and acid moiety with benzyl group. (ii) Coupling the resultant N6-trifluoro acetyl-L-Lysine benzyl ester with ethyl trans-f3-benzoyl acrylate, to yield the novel compound of the formula II, N2-[1 (8)-ethoxy carbonyl-3-oxo-3-phenyl propyl]-N6- trifluoro acetyl-L-Lysine benzyl ester. (iii) Reducing and de-benzylation N2_1- [1 (8) ethoxy carbonyl-3-oxo-3-phenyl propyl]-N6-trifluoro acetyl-L-Lysine benzyl ester hydrochloride by hydrogenation to yield N2_1-[1 (8) ethoxy carbonyl-3- phenyl propyl]-N6-trifluoro acetyl'-L-Lysine. (iv) Coupling the N2_1-[1 (8) ethoxy carbonyl-3-phenyl propyl]-N6-trifluoro acetyl-L-Lysine obtained in step (iii) with L- proline benzyl ester hydrochloride in the presence of 1-hydroxy benzotriazole and dicyclohexylcarbodiimide. (v) Debenzylating the N2_1-[1(8) ethoxy carbonyl- 3-phenyl propyl]-N6-trifluoro acetyl-L-Lysyl-L-proline benzyl ester by hydrogenation. (vi) Hydrolyzing the N2_1-[1(8) ethoxy carbonyl-3-phenyl propyl]- N6-trifluoro acetyl-L-Lysyl-L-proline to get Lisinopril dihydrate and. (vii) Purifying the Lisinopril dihydrate using Ion exchange resin Indion-225H to give pure Lisinopril dihydrate of the formula I. This application also discloses a novel intermediate N2-[1 (S)-ethoxy carbonyl-3- oxo-3-phenyl propyl]-N6-trifluoro acetyl-L-Lysine benzyl ester and a process for its preparation.