Dicyclohexylcarbodiimide → Perindopril Benzyl Ester

HRID 2308386Notes

Reaction equation

HRID 2308386 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:12]([O:19][C:20]([C@@H:22]1[CH2:30][C@H:29]2[C@H:24]([CH2:25][CH2:26][CH2:27][CH2:28]2)[NH:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:31][CH2:32][CH2:33][C@H:34]([NH:40][C@H:41]([C:43](O)=[O:44])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>C(OCC)(=O)C.C(N(CC)CC)C>[CH2:38]([O:37][C:35]([C@@H:34]([NH:40][C@@H:41]([CH3:42])[C:43]([N:23]1[C@@H:24]2[C@@H:29]([CH2:28][CH2:27][CH2:26][CH2:25]2)[CH2:30][C@H:22]1[C:20]([O:19][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:21])=[O:44])[CH2:33][CH2:32][CH3:31])=[O:36])[CH3:39]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 10015159(2S)-2-[[(2S)-1-ethoxy-1-oxopentan-2-yl]amino]propanoic acidHCID 115465001H-Indole-2-carboxylic acid, octahydro-, phenylmethyl ester, (2S,3aS,7aS)-, 4-methylbenzenesulfonate (1:1)

Product 1

HCID 11396975Perindopril Benzyl EsterYield 92%

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

There are introduced into a reactor, with stirring, 1 kg of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid benzyl ester para-toluenesulfonate, 0.06 kg of triethylamine, 4.6 liters of ethyl acetate and then, after stirring for 10 minutes at ambient temperature, 0.52 kg of N-[(S)-ethoxycarbonyl-1-butyl]-(S)-alanine, 0.15 kg of 1-hydroxybenzotriazole and 0.5 kg of dicylohexylcarbodiimide. The heterogeneous mixture is then brought to 30° C. for 3 hours while stirring well, and is subsequently cooled to 0° C. and filtered. The filtrate is then washed and subsequently evaporated to dryess to produce the expected product in a yield of 92%.

Workup

  1. additionThere are introduced into a reactor
  2. stirringwhile stirring well
  3. filtrationfiltered
  4. washThe filtrate is then washed
  5. customsubsequently evaporated

Sources & evidence

ORD record
ord-631e7cb7d98548b7819654019206b276
Source dataset
uspto-grants-2004_12
Patent number
US06835843B2

Reaction notes

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