5-Hydroxy-1,3-benzenedicarboxylic acid dimethyl ester (I) is treated with 3-amino-1,2-propanediol to give the corresponding bisamide (II), which is then iodinated with iodine monochloride. The reaction of the triiodinated compound thus obtained (III) with sodium methoxide and chloroacetic acid ethyl ester yields N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-5-[2-ethoxy-2-oxoethoxy]-1,3-benzenedicarboxamide (IV), which is treated with methylamine to give the 5-[2-(methylamino)-2-oxoethoxy] derivative (V). Iomeprol is obtained through a Smiles-type intramolecular rearrangement of (V) in aqueous alkaline medium.
Treatment of 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid (I) with thionyl chloride yields the dichloride (II). Compound (II) is treated with acetoxyacetyl chloride to give compound (III), which is methylated with iodomethane. Condensation with 3-amino-1,2-propanediol of the N-methyl derivative (IV) thus obtained, followed by deacetylation with alkali metal hydroxide, yields iomeprol.
In a different strategy, the target N-aryl hydroxy acetamide has been obtained by Smiles rearrangement of the aryloxy acetamide (I) under basic conditions.