Process for the preparation of perindopril

1. A process for the preparation of perindopril comprising condensing an N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II:

wherein X is a halide with an (2S,3aS,7aS)-2-carboxyperhydroindole of formula III:

wherein R is Si(R 1 )(R 2 )(R 3 ), and wherein R 1 , R 2 and R 3 are independently a straight or branched alkyl or aryl group having from 1 to about 25 carbon atoms.

2. The process of claim 1 , wherein the step of condensing is carried out in one or more organic solvents and in the presence of a base.

3. The process of claim 2 , wherein the organic solvent is one or more anhydrous solvents.

4. The process of claim 3 , wherein the one or more anhydrous solvents are selected from the group consisting of a chlorinated hydrocarbon, aromatic hydrocarbon, aliphatic hydrocarbon, cycloaliphatic hydrocarbon and mixtures thereof.

5. The process of claim 4 , wherein the chlorinated hydrocarbon is selected from the group consisting of dichloromethane, dichloroethane and mixtures thereof.

6. The process of claim 4 , wherein the aromatic hydrocarbon is selected from the group consisting of benzene, toluene, and mixtures thereof.

7. The process of claim 4 , wherein the aliphatic hydrocarbon is selected from the group consisting of hexane, heptane, and mixtures thereof.

8. The process of claim 4 , wherein the cycloaliphatic hydrocarbon is selected from the group consisting of cyclopentane, cyclohexane and mixtures thereof.

9. The process of claim 2 , wherein the base is an organic base selected from the group consisting of imidazole, triethylamine, diethylamine, pyridine, n-methyl, morpholine and mixtures thereof.

10. The process of claim 2 , wherein the base is present in a molar proportion of about 2 to about 5 moles per mole of the N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula III.

11. The process of claim 1 , wherein the N-[(S)-1-carbethoxybutyl]-(S)-alanyl halide of formula II is formed by reacting N-[(S)-1-carbethoxybutyl]-(S)-alanine with a halogenating agent in a suitable anhydrous solvent and in the presence or absence of an inert gas.

12. The process of claim 1 , wherein perindopril is thereafter converted to perindopril erbumine.

13. The process of claim 1 , further comprising treating perindopril with tert-butylamine to provide perindopril erbumine.

14. The process of claim 1 , further comprising adjusting the pH to about 4 to about 5 and subsequently reacting with tert-butylamine.

15. The process of claim 1 , further comprising purifying perindopril erbumine.