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

Participants

Reaction Steps

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.

Provenance & Evidence