141109-15-1Relevant articles and documents
Preparation method of sulfonic clopidogrel impurity
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Paragraph 0012; 0030-0031, (2020/08/02)
The invention discloses a preparation method of a sulfonic clopidogrel impurity. The preparation method comprises the following steps: reacting thiophene-2-ethanol with toluenesulfonyl chloride to generate p-toluenesulfonic acid-2-thienylethyl ester; carrying out esterification on o-chlorophenylglycine and methanol to generate o-chlorophenylglycine methyl ester; resolving the o-chlorophenylglycinemethyl ester by using L(+) tartaric acid; converting into free S-(+)-o-chlorophenylglycine methyl ester in dichloromethane; carrying out a condensation reaction on the p-toluenesulfonic acid-2-thienylethyl ester and the S-(+)-o-chlorophenylglycine methyl ester under an alkaline condition; acidifying the obtained product to generate (S)-2-(2-thienylethylamino)(2-chlorphenyl)methyl acetate, carrying out a condensation reaction on the (S)-2-(2-thienylethylamino)(2-chlorphenyl)methyl acetate and formaldehyde to obtain clopidogrel, and carrying out a reaction on the clopidogrel and chlorosulfonicacid to generate sulfonic clopidogrel impurity. The preparation method of the sulfonic clopidogrel impurity has the advantages of mild reaction conditions, accessible raw materials, low cost and highyield and purity.
A compound clopidogrel hydrogensulfate method for the preparation of
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, (2017/01/26)
The invention relates to a preparation method of clopidogrel disulfate. The preparation method comprises the following steps of step one. carrying out esterification reaction, namely preparing (+/-) DL-2-Chlorophenylglycine methyl ester; step two. carrying out splitting reaction, namely preparing (+) DL-2-Chlorophenylglycine methyl ester; step three. carrying out activating reaction, namely preparing alpha-thiophene ethanol p-toluenesulfonates; step four. carrying out substitution reaction, namely preparing (+) alpha-(2-thiophene ethylamino)-2-(2-chlorobenzene) methyl acetate hydrochloride; step five. carrying out ring closing reaction, namely preparing clopidogrel; and step six. carrying out salt-forming reaction, namely preparing the clopidogrel disulfate. The preparation method has the advantages that the preparation technology is optimized and improved, reaction conditions are mild, the splitting and the racemization are truly and synchronously carried out, and an obtained crude product has high specific rotation; a catalyst is used in the substitution reaction, so that the reaction time is shortened; the ring closing reaction is carried out at 40 DEG C under the condition of avoiding light, so that the purity of the product is relatively high; and the period of the whole synthetic route is shortened, the aftertreatment operation is simple, and therefore, the preparation method is suitable for mass production.