Piperazine Dihydrochloride → Irbesartan

HRID 659754

Reaction equation

HRID 659754 reaction equation
[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]#[N:24])=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:29][CH2:28][CH2:27][CH2:26]2)[N:6]=1)[CH2:2][CH2:3][CH3:4].[N-:30]=[N+:31]=[N-:32].[Na+].Cl.Cl.N1CCNCC1>C1(C)C(C)=CC=CC=1>[CH3:4][CH2:3][CH2:2][CH2:1][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[N:32]=[N:31][NH:30][N:24]=3)=[CH:13][CH:12]=2)[C:8](=[O:25])[C:7]2([CH2:26][CH2:27][CH2:28][CH2:29]2)[N:6]=1

Participants

5

Reactant 3

HCID 8893Piperazine DihydrochlorideHCID 33557Sodium AzideHCID 98431164'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

Product 1

HCID 3749IrbesartanYield 96%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Procedure

A mixture of 2-n-butyl-3-[(2′-cyanobiphenyl-4-yl)methyl]-1,3-diazaspiro-[4,4]-non-1-en-4-one (10 g), sodium azide (7.7 g) and piperazine dihydrochloride (7.5 g) in xylene (30 ml) was refluxed for 7 hours under stirring. The reaction was cooled to room temperature and extracted with 5% NaOH solution. The pooled alkaline solution was washed with toluene or xylene (15 ml) and the aqueous phase neutralized to pH 6.5 using concentrated HCL. The resulting suspension was stirred for 3 hours at room temperature and filtered obtain irbesartan (3.6 g, 96% purity by HPLC).

Workup

  1. temperaturewas refluxed for 7 hours
  2. extractionextracted with 5% NaOH solution
  3. washThe pooled alkaline solution was washed with toluene or xylene (15 ml)
  4. concentrationusing concentrated HCL
  5. stirringThe resulting suspension was stirred for 3 hours at room temperature
  6. filtrationfiltered

Sources & evidence

ORD record
ord-a67296b3abe540c4a17ddd7e7fd19fb6
Source dataset
uspto-grants-2011_12
Patent number
US08080670B2

Linked notes

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