The preparation method of the isomer of trandolapril intermediate

Abstract

The invention discloses a preparation method of an isomer of a trandolapril intermediate, and in particular discloses a preparation method of the isomer of the trandolapril intermediate which is shown in a formula C and is acquired by using (R,S,S)-octahydroindole-2-carboxylic acid (shown in a formula A) as an initial raw material with the content of more than 90 percent, performing configuration turning and upper benzyl protection to obtain isomer mixtures C and D of the corresponding trandolapril intermediate and performing separation again. According to the technical scheme, the formula A is subjected to configuration turning, and the content of a compound of the formula B is obviously increased, so that the isomers of the subsequent other intermediates are greatly prepared, and the compound is used for preparing medicines for resisting cardiovascular disease and controlling the quality of the medicines.

Description

technical field

[0001] The invention belongs to the field of biomedicine, and specifically relates to (R, S, S)-octahydroindole-2-carboxylic acid (shown in formula A) with a content higher than 90% as a starting material, which is reversed in configuration, up The benzyl group is protected to obtain the corresponding isomer mixtures C and D of the trandapril intermediate, and then separated to obtain the preparation method of the isomer of the trandapril intermediate shown in formula C. Background technique

[0002] Trandolapril (Trandolapril) (as shown in formula E) is developed by Roussel Uclaf Company of Germany, a kind of long-acting angiotensin-converting enzyme inhibitor (ACE1) produced by Sanofi-Aventis Company of France, listed in France in 1993 , for the treatment of hypertension, congestive heart failure and myocardial infarction.

[0003]

[0004] Trandolapril contains 5 chiral centers, so the isomer control of intermediates in its preparation process and the ...

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