Preparation method of contrast medium intermediate triodoisophthalolyl chloride

Abstract

The invention discloses a preparation method of a contrast medium intermediate triodoisophthalolyl chloride. The preparation method comprises the following steps: adding 5-amino-2,4,6-triiodoisophthalic acid, thionyl chloride and DMF (Dimethyl Formamide) to isobutyl acetate, after a heating reaction, cooling and pouring the reaction liquid in ice water, adding a saturated sodium bicarbonate solution until the pH value is up to 11-13, separating out yellow solid and filtering, using isobutyl acetate to recrystallize and purify the solid, drying the solid to obtain 5-Amino-2,4,6-triodoisophthalolyl chloride. The method is simple, convenient and easy to operate, can greatly increase the total yield and the product purity compared with the original method; the post treatment is simple to operate and efficient. The alkaline DMF added in the step can be removed with water in the post treatment, so that the method is simple and convenient; a little amount of isobutyl acetate is utilized to recrystallize the solid to obtain the purified product; the purity of the final product is up to 99.5% through detection of HPLC (High Performance Liquid Chromatography).

Description

technical field [0001] The invention specifically relates to a preparation method of a contrast agent intermediate triiodoisophthaloyl chloride. Background technique [0002] X-ray contrast agent is an important diagnostic drug in X-ray diagnostics. Among them, non-ionic contrast agents such as iohexol, iopamidol, and ioversol are the most widely used and fastest-growing, and have been widely used in urinary tract, blood vessels, ventricles, ventricles, lymphatic channels, and gastrointestinal contrast agents. It can be used for contrast examination of many lesions in CT examination, and has the characteristics of high contrast density, low toxicity and stable performance. [0003] Most non-ionic contrast agents are synthesized from 5-amino-2,4,6-triiodoisophthalic acid chloride in many cases. For example, in the synthesis method of iopamidol reported in British Patent GB1472050, Iopamidol is synthesized by 5-amino-2,4,6-triiodoisophthalic acid chloride, the preparation me...

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Problems solved by technology

[0006] This method is carried out in thionyl chloride without solvent, which will cause serious industrial safety problems. On the one hand, it is difficult to add the solid starting product step by step to hot thionyl chloride. On the other hand, On the one hand, the feeding method of cold mixing and continuous heating of the two reagents will produce short-term reactions and bring unforeseen effects

After thermal decomposition of thionyl chloride, sulfur dioxide and hydrogen chloride gas are generated, causing air pollution

Moreover, the method in the above-mentioned patent slowly adds thionyl chloride step by step, and the operation process is more complicated, which is not conducive to industrial expansion of production.

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