A kind of recycling process of clopidogrel bisulfate splitting mother liquor

Abstract

The invention relates to a recovery and treatment process for splitting mother liquor of clopidogrel hydrogen sulfate, and belongs to the technical field of chemical waste liquid treatment. The recovery treatment process is to add dilute hydrochloric acid to adjust the pH value in the mother liquor of the clopidogrel bisulfate resolution step (that is, the water layer containing the dextro-isomer), then add an organic solvent for extraction, and obtain the organic phase, then add solid acid to the organic system, reflux for several hours, filter while hot into another reactor, and then evaporate a certain amount of organic solvent under reduced pressure, then cool down, filter, collect solids, and dry to obtain racemic (R,S)‑2‑(2‑chlorophenyl)‑2‑(4,5,6,7‑tetrahydrothiophene[3,2‑c]pyridine‑5) methyl acetate hydrochloride.

Description

technical field [0001] The invention relates to a process for recovering and treating clopidogrel hydrogen sulfate mother liquor, and belongs to the technical field of chemical waste liquid treatment. Background technique [0002] Clopidogrel bisulfate is a new type of thienopyridine derivatives, which can irreversibly inhibit the aggregation of platelets by selectively binding to the ADP receptors coupled with adenylase on the surface of platelets, and can reduce the occurrence of thrombus in blood vessels. It is mainly used clinically to prevent myocardial infarction, acute coronary syndrome, atherosclerotic disease, prevent in-stent restenosis and thrombotic complications after coronary stent implantation. [0003] At present, the industrial synthesis process of domestic clopidogrel hydrogen sulfate mainly uses 2-bromo-2-(2-chlorophenyl)methyl acetate and 4,5,6,7-tetrahydrothiophene [3,2 -c]pyridine is the starting material, wherein: patent CN201510173616 discloses a met...

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Problems solved by technology

[0003] At present, the industrial synthesis process of domestic clopidogrel hydrogen sulfate mainly uses 2-bromo-2-(2-chlorophenyl)methyl acetate and 4,5,6,7-tetrahydrothiophene [3,2 -c]pyridine is the starting material, wherein: patent CN201510173616 discloses a method for synthesizing clopidogrel bisulfate using a novel catalyst ionic liquid, but the preparation cost of the ionic liquid catalyst is high, it is difficult to reuse, and the production cycle A series of defects such as long limit its scale-up production; patent 201710656966 discloses an industrial production process that first synthesizes the racemate clopidogrel base, then chemically splits it, and finally becomes sulfate, although the process operation is slightly complicated , but its low cost, mild reaction, short production cycle and other advantages make it still have a good industrialization prospect, but people in the industry know that we can only get half of the yield of raw materials in the chemical split step, how to recycle the rest The other half of by-products (clopidogrel bisulfate resolution mother liquor) have great research value for this process