Process for the purification of an intermediate
AssigneeFructamine S.p.A.
InventorNicola Desantis
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Abstract
This invention refers to a new process for the synthesis of (S)-N,N'-bis(2-hydroxy-1-(hydroxymethyl)ethyl!-5-(2-hydroxy-1-oxopropyl! amino!-2,4,6-triiodo-1,3-benzendicarboxamide, of formula (III), ##STR1## starting from 5-amino-2,4,6-triiodo-1,3-benzendicarboxylic acid dichloride characterized by a new step of chromatographic purification through resins of (S)-5-2-(acetyloxy)-1-oxopropyl!amino!-2,4,6-triiodo-1,3-benzendicarboxy lic acid dichloride, which enables the direct conversion to the compound of formula (III), without preventive isolation.
Claims12
Process for the preparation of (S)-N,N'-bis(2-hydroxy-1-(hydroxymethyl)ethyl!-5-(2-hydroxy-1-oxopropyl! amino!-2,4,6-triiodo-1,3-benzendicarboxamide according to Scheme 1, comprising the following steps:
- ##STR4## a) reaction of the compound of formula (I), 5-amino-2,4,6-triiodo-1,3-benzendicarboxylic acid dichloride with S-(-)-2-(acetyloxy)!propionic chloride in dimethylacetamide in order to give a solution of the compound of formula (II), (S)-5-2-(acetyloxy)-1-oxopropyl!amino!-2,4,6-triiodo-1,3-benzendicarboxy lic acid dichloride in dimethyl-acetamide;
- b) elution of the resulting solution of step a) from porous and/or macroporous cross-linked resins, anionic and cationic, anionic resins as free base form, cationic resins as sodium salt form, with the proviso that the system constituted by said solution and resin contains a water amount which can hydrolyze the excess of S-(-)-2-(acetyloxy)!propionic acid chloride, but which does not hydrolyze the dichloride of compound (II);
- c) possible water elimination from the resulting solution of step b) up to a content of 0-2%;
- d) reaction with serinol at a temperature of 0.degree.-10.degree. C. for 5-20 h;
- e) isolation of the compound of formula (III).
Dependencies are inferred from the claim text.