A CaCl2 solution was prepared by dissolving CaCl2.2H2O (233 kg) in water (723 kg). A 3-chloro-1,2-propanediol (CPD) solution was prepared by dissolving 3-chloro-1,2-propanediol (176 kg) in water (176 kg). The 4000 L glass-lined reactor was charged with water (907 kg) and 5,5′-[(1,3-dioxo-1,3-propanediyl)diimino]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] (563 kg). The pH of the slurry was adjusted to 5.5 to 7.0 with 37% HCl or 30% NaOH as needed. 50% NaOH solution (128 kg) was charged to the reaction mixture while maintaining its temperature to <30° C. The CaCl2/water solution and then the CPD/water solution were each charged to the reaction mixture. The reaction mixture was then heated at 50° C. and stirred for 6 hours. 50% NaOH was added as needed to maintain the pH of the reaction at 10. When the reaction was complete, acetic acid (28 kg) was added to adjust the pH of the reaction mixture to 5. Using a jacket temperature of 75° C., water (1682 kg) was distilled off under vacuum. While cooling to 10° C., ethanol (2585 kg) was added to the residue in the reaction vessel. After stirring at 10° C. for 2 hours, the crude solid was collected by filtration. The solids were washed with ethanol (500 kg). The crude solid was dried at 55° C. under vacuum to give 783 kg of crude 5,5′-[(1,3-dioxo-1,3-propanediyl)bis[(2,3-dihydroxypropyl)imino]]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide]. The crude product contained 55% w/w 5,5′-[(1,3-dioxo-1,3-propanediyl)bis[(2,3-dihydroxypropyl)imino]]bis[N-(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide] which had a chromatographic purity of 77 area %.
