Water → 4'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

HRID 1275805

Reaktionsgleichung

Reaktionsgleichung von HRID 1275805
Cl.[CH2:2]([CH:6]1[NH:10][C:9](=[O:11])[C:8]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[NH:7]1)[CH2:3][CH2:4][CH3:5].Br[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([C:30]#[N:31])=[CH:26][CH:27]=[CH:28][CH:29]=2)=[CH:20][CH:19]=1.O.ClCCl>C1(C)C=CC=CC=1>[CH2:2]([C:6]1[N:10]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]3[C:25]([C:30]#[N:31])=[CH:26][CH:27]=[CH:28][CH:29]=3)=[CH:22][CH:23]=2)[C:9](=[O:11])[C:8]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[N:7]=1)[CH2:3][CH2:4][CH3:5]

Komponenten

6

Edukt 4

HCID 962WaterHCID 6344DichloromethaneHCID 15019124'-(Bromomethyl)-2-cyanobiphenylHCID 221178832-Butyl-1,3-diazaspiro[4.4]nonan-4-one hydrochloride

Produkt 1

HCID 98431164'-((2-Butyl-4-oxo-1,3-diazaspiro(4.4)non-1-ene-3-yl)methyl)(1,1'-biphenyl)-2-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

A preferred embodiment of the process comprises reacting a 2-butyl-1,3-diazaspiro[4.4]nonan-4-one hydrochloride and 4'-(bromomethyl)[1,1'-biphenyl]-2-carbonitrile in a water-immiscible organic solvent such as dichloromethane or toluene, in the presence of methyl-tributylammonium chloride and aqueous sodium or potassium hydroxide, separating the organic phase of dichloromethane or toluene, washing the separated organic phase with water, optionally drying the organic phase over a desiccant, filtering the organic phase, evaporating the organic phase to an oily residue and finally crystallizing the oily residue from an organic solvent, such as methyl tert butyl ether to give 4'-[[2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3yl]methyl][1,1'-biphenyl]-2-carbonitrile. This compound is an intermediate in the synthesis of the compound 2-butyl-3-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1,3-diazaspiro[4.4]non-1-en-4-one known by the trademark (Irbesartan) and can be easily converted to Irbesartan and its salts according to the process described in U.S. Pat. No. 5,270,317. The compound Irbesartan antagonizes the action of angiotensin II.

Aufarbeitung

  1. customin the presence of methyl-tributylammonium chloride and aqueous sodium or potassium hydroxide, separating the organic phase of dichloromethane or toluene
  2. washwashing the separated organic phase with water
  3. customoptionally drying the organic phase over a desiccant,
  4. filtrationfiltering the organic phase
  5. customevaporating the organic phase to an oily residue
  6. customfinally crystallizing the oily residue from an organic solvent

Quellen und Nachweise

ORD-Eintrag
ord-e3447eb4092c4271a6eabf7ea73bff78
Quelldatensatz
uspto-grants-2000_12
Patentnummer
US06162922

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