Sodium Hydroxide → Iopamidol

Participants

Reaction Steps

(S)-2-(Acetyloxy)propanoyl chloride (16.5 g, 110 mmol) is added, over 20 min, to a stirred solution of N,N′-bis[2-acetyloxy-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide (53.3 g, 61.1 mmol) in N,N-dimethylacetamide (75 mL) while keeping the temperature of the reaction mixture below 30° C. A further amount of (S)-2-(acetyloxy)propanoyl chloride (0.9 g, 6.0 mmol) is added after 24 and 30 hours and the reaction mixture is stirred at the same temperature for additional 15 hours. 5 M NaOH (90 mL, 450 mmol) is dripped over a period of 2 hours into the reaction mixture vigorously stirred at 45° C. After two hours the mixture is concentrated under vacuum and reintegrated with additional N,N-dimethylacetamide (200 mL). After two hours at room temperature the resulting suspension is filtered and the solid washed with N,N-dimethylacetamide (2×20 mL). The mother liquors, combined with the washings, are concentrated to an oily residue, which is diluted with water (200 mL) and nanofiltered. The retentate is loaded onto an Amberlite® XAD-16.00 resin column (160 mL) that is eluted with water. The eluate is concentrated and loaded onto two ion exchange resin columns (Dowex® C350 15 mL, Relite® MG1 10 mL). The eluate is concentrated and the solid residue is crystallized from ethanol to afford Iopamidol (41.2 g, 53 mmol).

Provenance & Evidence