Acetonitrile → Perindopril

HRID 900395Notes

Reaction equation

HRID 900395 reaction equation
[NH2:1][C@@H:2]([CH2:8][CH2:9][CH3:10])[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(N(CC)CC)C.C(#N)C.Br[C@H:22]([CH3:37])[C:23]([N:25]1[C@@H:33]2[C@@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:27][C@H:26]1[C:34]([OH:36])=[O:35])=[O:24]>ClCCl>[CH2:6]([O:5][C:3]([C@@H:2]([NH:1][C@@H:22]([CH3:37])[C:23]([N:25]1[C@@H:33]2[C@@H:28]([CH2:29][CH2:30][CH2:31][CH2:32]2)[CH2:27][C@H:26]1[C:34]([OH:36])=[O:35])=[O:24])[CH2:8][CH2:9][CH3:10])=[O:4])[CH3:7]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 10080526ethyl (2S)-2-aminopentanoateHCID 69309500(2S,3aS,7aS)-1-[(2R)-2-bromopropionyl]octahydro-1H-indole-2-carboxylic acid

Product 1

HCID 107807Perindopril

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Introduce into a reactor 105 g of ethyl (2S)-2-aminopentanoate, 135 ml of triethylamine and 135 ml of acetonitrile, and then bring the mixture to 60° C. and slowly add a solution of 200 g of the compound obtained in Step A in 1.3 liters of dichloromethane, and subsequently reflux for 4 hours. After returning to ambient temperature, wash the mixture with water and with a dilute acetic acid solution, and then evaporate off the solvents to yield (2S,3aS,7aS)-1-{(2S)-2-[(1S)-1-(ethoxycarbonyl)butylamino]propionyl}octahydro-1H-indole-2-carboxylic acid.

Workup

  1. customto 60° C.
  2. temperaturesubsequently reflux for 4 hours
  3. customAfter returning to ambient temperature
  4. washwash the mixture with water
  5. customwith a dilute acetic acid solution, and then evaporate off the solvents

Sources & evidence

ORD record
ord-d92e81cc91174b3ba07886127e3813fb
Source dataset
uspto-grants-2008_04
Patent number
US07358372B2

Reaction notes

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