Sodium Hydroxide → Iopamidol

HRID 1797449Notes

Reaction equation

HRID 1797449 reaction equation
C([O:4][C@@H:5]([CH3:9])[C:6](Cl)=[O:7])(=O)C.C([O:13][CH2:14][CH:15]([NH:21][C:22]([C:24]1[C:29]([I:30])=[C:28]([NH2:31])[C:27]([I:32])=[C:26]([C:33]([NH:35][CH:36]([CH2:42][O:43]C(=O)C)[CH2:37][O:38]C(=O)C)=[O:34])[C:25]=1[I:47])=[O:23])[CH2:16][O:17]C(=O)C)(=O)C.[OH-].[Na+]>CN(C)C(=O)C>[CH3:9][C@H:5]([OH:4])[C:6]([NH:31][C:28]1[C:29]([I:30])=[C:24]([C:22]([NH:21][CH:15]([CH2:16][OH:17])[CH2:14][OH:13])=[O:23])[C:25]([I:47])=[C:26]([C:33]([NH:35][CH:36]([CH2:42][OH:43])[CH2:37][OH:38])=[O:34])[C:27]=1[I:32])=[O:7]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetate2×HCID 11766168N,N'-Bis[2-(acetyloxy)-1-[(acetyloxy)methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide

Product 1

HCID 65492IopamidolYield 87%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

(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).

Workup

  1. customthe temperature of the reaction mixture below 30° C
  2. stirringvigorously stirred at 45° C
  3. concentrationAfter two hours the mixture is concentrated under vacuum
  4. filtrationAfter two hours at room temperature the resulting suspension is filtered
  5. washthe solid washed with N,N-dimethylacetamide (2×20 mL)
  6. concentrationare concentrated to an oily residue, which
  7. additionis diluted with water (200 mL)
  8. washis eluted with water
  9. concentrationThe eluate is concentrated and loaded onto two ion exchange resin columns (Dowex® C350 15 mL, Relite® MG1 10 mL)
  10. concentrationThe eluate is concentrated
  11. customthe solid residue is crystallized from ethanol

Sources & evidence

ORD record
ord-78c5e9a995204623bc148dc0f4184ba9
Source dataset
uspto-grants-2006_04
Patent number
US07034183B2

Reaction notes

Loading…