The title compound is prepared by condensation of the acetamido isophthalamide (I) with epichlorohydrin (II) in 2-methoxyethanol.
In an improved method, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent alkylation of (II) with 1-chloro-3-methoxy-2-propanol (III) yields regioselectively the N-alkylated acetamide (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.
In a different strategy, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent condensation of (II) with epichlorohydrin (III) yields the dimeric adduct (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.
In an improved method, the acetamido isophthalamide (I) is treated with boric acid and KOH to form the cyclic diborate tripotassium salt (II). Subsequent alkylation of (II) with 2-chloroethanol (III) yields regioselectively the N-alkylated acetamide (IV). The borate groups of (IV) are finally removed upon quenching with diluted HCl.
In an alternative method, the tetra-acid chloride (I) derived from O-acetyl-iodixanol is condensed with 3-amino-1,2-propanediol (II) under Schotten-Baumann conditions to afford amide (III). The acetate ester group of (III) is then removed by acidic hydrolysis to furnish the title compound.