141109-18-4Relevant articles and documents
Preparation method of clopidogrel hydrogen sulfate intermediate
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Paragraph 0032; 0035-0073; 0083, (2021/05/15)
The present invention relates to a preparation method of a clopidogrel hydrogen sulfate intermediate. (+)-2-chlorophenylglycine methyl ester and alpha-thiopheneethanol p-toluenesulfonate are adopted as raw materials, a reaction solvent and an acid-binding agent are added for a condensation reaction, the condensation reaction process is divided into a first stage and a second stage, and when 60-95% of the condensation reaction is completed, first-stage reaction is completed; after the first-stage reaction is completed, firstly part of the reaction solvent is removed, and then second-stage reaction is carried out; and after the second-stage reaction is completed, a target product is obtained, namely the clopidogrel hydrogen sulfate intermediate. After the first-stage reaction is completed, part of the reaction solvent is removed firstly, and then the second-stage reaction is continued, so that the concentration of the reaction material can be increased in the later stage of the condensation reaction, the use amount of the reaction solvent is reduced, and racemization and side reaction in the reaction process are effectively inhibited, thereby improving the chiral purity of the product, increasing the yield, reducing the use of auxiliary materials greatly, and reducing the production cost.
Synthesis of clopidogrel intermediate (S)-2-(2- thiophene ethylamine-)-(2-chlorophenyl)- methyl acetate
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Paragraph 0050-0133, (2020/03/17)
The invention belongs to the technical field of medicines, and relates to a novel process (S)- 2 - (2 - for synthesizing the intermediate) - (2 - thiophene ethyl amino) - chlorophenyl, methyl acetate and the salt thereof, for the first time, and the inven
Method for preparing D-(+)-alpha-(2-thiopheneethylamino)-alpha-(2-chlorophenyl)methyl acetate hydrochloride
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Paragraph 0011; 0061-0064; 0070-0072; 0079; 0084-0108, (2018/12/14)
The invention provides a novel method for preparing D-(+)-alpha-(2-thiopheneethylamino)-alpha-(2-chlorophenyl)methyl acetate hydrochloride, aiming at solving the technical problems of a traditional synthesis technology of the D-(+)-alpha-(2-thiopheneethylamino)-alpha-(2-chlorophenyl)methyl acetate hydrochloride that the technology is complicated, the cost is high and the yield is low. The method comprises the following steps: 1) preparing 2-bromothiophene; 2) preparing 2-thiopheneethanol; 3) preparing 2-thiopheneethanol p-toluenesulfonate; 4) preparing L-(+)-o-chlorophenylglycine methyl esterL-tartrate; 5) preparing the D-(+)-alpha-(2-thiopheneethylamino)-alpha-(2-chlorophenyl)methyl acetate hydrochloride. The preparation method provided by the invention is low in cost, high in yield andhigh in safety and is suitable for industrial production.