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US 5,705,692 AGranted
Process for the preparation of iohexol
AssigneeAbbott Laboratories
InventorsXiu C. Wang, Steve A. Chamberlin, Ashok V. Bhatia, Gregg E. Robinson, John Hufnagel
Life of this patent
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Abstract
Provided is a novel process for the preparation of iohexol having improved yields and purity, reduced number of isolated intermediates, and significantly reduced volume of ion-exchange resins required to desalinate the final product.
Claims16
A process for making iohexol comprising the steps of:
- a. combining 5-amino-2,4,6-triiodoisophthalic acid dichloride, acetyl halide, and a solvent selected from N,N-dimethylacetamide, dimethylformamide, or 1-methyl-2-pyrrolidone to form a first reaction mixture;
- b. maintaining the first reaction mixture for a period of time sufficient to allow the reaction to proceed to completion;
- c. combining 3-amino-1,2-propanediol, N,N-dimethylacetamide, and a base with the first reaction mixture to form a second reaction mixture;
- d. maintaining the second reaction mixture for a period of time sufficient for 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide formation;
- e. converting 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide to iohexol in the presence of 3-chloro-1,2-propanediol or 3-bromo-1,2-propanediol, base and alcohol;
- and
- f. isolating the iohexol.
4 more elements
A process for making iohexol comprising the steps of:
- a. combining 5-amino-2,4,6-triiodoisophthalic acid dichloride, acetyl chloride and N,N-dimethylacetamide to form a first reaction mixture;
- b. maintaining the first reaction mixture for four to eighteen hours to allow the reaction to proceed to completion;
- c. combining 3-amino-1,2-propanediol, N,N-dimethylacetamide, and lithium hydroxide with the first reaction mixture to form a second reaction mixture;
- d. maintaining the second reaction mixture for six to eighteen hours to form 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide;
- e. adding the reaction mixture to ethyl acetate and isopropanol to precipitate the 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide;
- f. converting the 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide to iohexol in the presence of lithium hydroxide and methanol;
- and
- g. isolating the iohexol.
5 more elements
A process for making 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide comprising the steps of:
- a. combining 5-amino-2,4,6-triiodoisophthalic acid dichloride, acetyl halide, and a solvent selected from N,N-dimethylacetamide, dimethylformamide, or 1-methyl-2-pyrrolidone to form a first reaction mixture;
- b. maintaining the first reaction mixture for a period of time sufficient to allow the reaction to proceed to completion;
- c. combining 3-amino-1,2-propanediol, N,N-dimethylacetamide, and a base with the first reaction mixture to form a second reaction mixture;
- d. maintaining the second reaction mixture for a period of time sufficient for 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide formation;
- e. isolating the 5-acetamino-N,N'-bis-(2,3-dihydroxy-propyl)-2,4,6-triiodobenzene dicarboxamide so formed.
2 more elements
Dependencies are inferred from the claim text.