Novel method for synthesising perindopril and the pharmaceutically acceptable salt thereof

A process for the synthesis of perindopril of formula (I):

• and pharmaceutically acceptable salts thereof,
• wherein 1-(1-cyclohexen-1-yl)-pyrrolidine of formula (II):
• is reacted with a compound of formula (III):
• wherein R1 represents a protecting group and R2 represents a protecting group,
• to yield the compound of formula (IV):
• the amine function of the compound of formula (IV) is deprotected and the deprotected intermediate thus obtained is subjected to dehydration, to yield a compound of formula (V):
• or an addition salt thereof with a mineral or organic acid,
• which is reacted with the compound of formula (VI):
• in ethyl acetate,
• in the presence of an amount of 1-hydroxybenzotriazole of from 0.4 to 0.6 mol per mol of compound of formula (V) used and an amount of dicyclohexylcarbodiimide of from 1 to 1.2 mol per mol of compound of formula (V) used,
• in the presence of an amount of triethylamine of from 0.25 to 1.2 mol per mol of compound of formula (V) used,
• at a temperature of from 20 to 77° C.,
• to yield, after isolation, the compound of formula (VII):
• which is hydrogenated in the presence of a catalyst,
• under a hydrogen pressure of from 1 to 30 bars, to yield, after deprotection of the acid function, perindopril of formula (I), which is converted, if desired, into a pharmaceutically acceptable salt.