Tert-Butylamine → (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic Acid Benzyl Ester

HRID 2243113Notes

Reaction equation

HRID 2243113 reaction equation
[CH3:1][CH2:2][CH2:3][C@H:4]([NH:10][C@H:11]([C:13]([N:15]1[C@H:23]([C:24]([OH:26])=[O:25])[CH2:22][C@H:21]2[C@@H:16]1[CH2:17][CH2:18][CH2:19][CH2:20]2)=[O:14])[CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:27](N)([CH3:30])([CH3:29])[CH3:28].[C:32]([C@@H:37](N[C@H](C(O)=O)C)[CH2:38]CC)(OCC)=O.ON1C2C=CC=CC=2N=N1>C(N(CC)CC)C>[CH3:1][CH2:2][CH2:3][C@H:4]([NH:10][C@H:11]([C:13]([N:15]1[C@@H:23]([C:24]([O:26][CH2:28][C:27]2[CH:30]=[CH:38][CH:37]=[CH:32][CH:29]=2)=[O:25])[CH2:22][C@H:21]2[C@@H:16]1[CH2:17][CH2:18][CH2:19][CH2:20]2)=[O:14])[CH3:12])[C:5]([O:7][CH2:8][CH3:9])=[O:6]

Participants

6

Reactant 4

HCID 6385Tert-ButylamineHCID 757711-HydroxybenzotriazoleHCID 107807PerindoprilHCID 10015159(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoic acid

Product 1

HCID 71751530(2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-(Ethoxycarbonyl)butyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic Acid Benzyl Ester

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

EP 308 341 teaches an improved large-scale synthesis of perindopril in the form of the t-butylamine salt. (2S,3aS,7aS)-octahydroindole-2-carboxylic acid benzyl ester p-toluensulfonic salt and N-((S)-1-carbethoxybutyl)-L-alanine are reacted in the presence of triethyl amine, N,N-dicyclohexylcarbodiimide and 1-hydroxybenztriazole. After completion of the reaction, perindopril benzyl ester is obtained, which is reduced, lyophilized and then converted into a salt with t-butylamine in ethyl acetate.

Workup

  1. customAfter completion of the reaction

Sources & evidence

ORD record
ord-f4b47a6cf82048779a2ded8c9aefcf66
Source dataset
uspto-grants-2010_03
Patent number
US07674814B2

Reaction notes

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