Improved process for preparation of highly pure trandolapril
The present invention provides an improved process for preparation of highly pure trandolapril. The process comprises of the following steps: (i) crystallization of mixture of racemic benzyl trans-(2S, 3aR, 7aS)-octahydro-1H-indole carboxylate p-toluene sulphonic acid salt (IIa.p-TsOH) and benzyl tr...
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Main Authors | , , , |
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Format | Patent |
Language | English |
Published |
17.08.2006
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Subjects | |
Online Access | Get full text |
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Summary: | The present invention provides an improved process for preparation of highly pure trandolapril. The process comprises of the following steps: (i) crystallization of mixture of racemic benzyl trans-(2S, 3aR, 7aS)-octahydro-1H-indole carboxylate p-toluene sulphonic acid salt (IIa.p-TsOH) and benzyl trans-(2R, 3aS, 7aR)-octahydro-1H-indole carboxylate p-toluene sulphonic acid salt (IIb.p-TsOH) through appropriate selection of solvents to enrich the purity to >99% from a mixture containing the other diastereomers (IIc-h.p-TsOH) up to 6%, (ii) optical resolution of racemic mixture of benzyl trans-(2S, 3aR, 7aS)-octahydro-1H-indole carboxylate (Na) and benzyl trans-(2R, 3aS, 7aR)-octahydro-1H-indole carboxylate (lib) with (-)-dibenzoyl-L-tartaric acid monohydrate in an appropriately selected solvents and temperature, (iii) reaction of benzyl ester Ma with N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanine N-carboxy anhydride (III a, NEPA-NCA hereafter) to get trandolapril benzyl ester (IVa), and finally (iv) crystallization of crude trandolapril from appropriate solvents. |
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Bibliography: | Application Number: AU20050327440 |