![methyl-(S)-alpha-(2-chlorophenyl)-6,7-dihydro-thieno[3,2-c]pyridine-5(4H)-acetate camphor sulphonate](/Databaselist/images/loading.webp)
113665-84-2Relevant academic research and scientific papers
Modified asymmetric strecker reaction of aldehyde with secondary amine: A protocol for the synthesis of S-clopidogrel (an antiplatelet agent)
Sadhukhan, Arghya,Saravanan,Khan, Noor-Ul H.,Kureshy, Rukhsana I.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 7076 - 7080 (2012)
A first approach for catalytic asymmetric Strecker reaction of aldehydes with a secondary amine in the presence of sodium fluoride using hydroquinine as chiral catalyst was developed. The catalytic system gave α-aminonitriles in excellent yields (up to 95
Iridium and bis(4-nitrophenyl)phosphoric acid catalysed amination of diol by hydrogen-borrowing methodology for the synthesis of cyclic amine: Synthesis of clopidogrel
Swain, Sharada Prasanna,Shri, Om,Ravichandiran
, (2021)
The borrowing hydrogen method is an environmentally benign process for the synthesis of amines, as H2O is the side product. A new green process for the amination of diol by [Ir] catalyst 15 and bis(4-nitrophenyl)phosphoric acid for the synthesis of cyclic amine is reported. This method was successfully applied for the synthesis of antiplatelet drug clopidogrel.
Synthetic improvements in the preparation of clopidogrel
Wang, Lixin,Shen, Jianfen,Tang, Yi,Chen, Yi,Wang, Wen,Cai, Zegui,Du, Zhenjun
, p. 487 - 489 (2007)
Synthetic improvements in the preparation of clopidogrel are described. The synthesis was accomplished in four steps or one-pot in above 70% overall yield. The process featured PTC catalyzed alkaline hydrolysis of the key intermediate 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetonitrile and highly effective kinetic resolution of racemic clopidogrel using L-camphorsulphonic acid in toluene and has been successfully used in a 50-kg pilot test.
A facile solid-phase synthesis of (+)-(S)-clopidogrel
Jung, Kiwon,Kim, Jae-Sun,Kim, Tae-Hyun,Kim, Jinwoong
, p. 326 - 329 (2013)
Enantiomerically pure (+)-(S)-clopidogrel was prepared by solid-phase synthesis using the commercially available Wang resin. This method offers mild reaction conditions and provides the (+)-(S)-clopidogrel in overall 52% yield over six steps and with optical purity of 98.0% ee. Copyright
Copper (II) bromide catalysed one pot bromination and amination for the green, cost-effective synthesis of clopidogrel
Kumar, K. Naveen,Mhate, Mouzma,Panchami, Hirave,Ravichandiran, V.,Swain, Sharada Prasanna
, (2022/03/15)
Copper (II) bromide catalyzed one pot α-bromination and followed by amination of a benzylic ester is reported. The α-bromination of ester by copper (II) bromide generates copper (I) bromide and HBr. The copper (I) bromide is oxidized to copper (II) bromide by N-Methylmorpholine-N-Oxide (NMO) in presence of HBr. The amines undergo nucleophilic substitution reaction with α-brominated ester compound. This methodology was applied for the synthesis of the familiar antiplatelet drug clopidogrel. This green process is an alternate to classical methods for the synthesis of clopidogrel, which requires, generates stochiometric amount of brominating agents and HBr, respectively.
Preparation method of clopidogrel hydrogen sulfate and intermediate N-(2-thiopheneethyl) methyleneimine of clopidogrel hydrogen sulfate
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Paragraph 0109; 0115, (2021/05/08)
The invention discloses a preparation method of clopidogrel hydrogen sulfate and an intermediate N-(2-thiophene ethyl) methyleneamine of the clopidogrel hydrogen sulfate. The synthesis method of the intermediate comprises the step of carrying out an Eschweiler-Clarke methylation reaction by taking 2-thiophene ethylamine and paraformaldehyde as raw materials to obtain the N-(2-thiophene ethyl) methyleneamine. The invention also provides a method for preparing clopidogrel hydrogen sulfate. According to the synthesis method provided by the invention, the required solid product (N-(2-thiopheneethyl) methyleneimine) is synthesized in one step, the synthesis method is simple, the qualified solid compound is directly obtained, the time and the raw material cost are saved, the storage and the transportation are convenient, the purity is good, the yield is high, and the synthesis method is suitable for industrial production.
Preparation method of clopidogrel hydrogen sulfate crystal form II
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Paragraph 0044; 0054; 0058; 0070; 0073, (2020/02/29)
The invention discloses a preparation method of a clopidogrel hydrogen sulfate crystal form II. The method includes: preparation of (+)o-chlorophenylglycine methyl ester; preparation of (+)alpha-(2-thiophene ethylamino)-alpha-(2-chlorphenyl)methyl acetate hydrochloride; preparation of (+)clopidogrel free alkali; preparation of (+)clopidogrel camphorsulfonic acid double salt; hydrolysis of (+)clopidogrel camphorsulfonic acid double salt; and preparation of clopidogrel hydrogen sulfate. The preparation method of the clopidogrel hydrogen sulfate crystal form II provided by the invention optimizesthe synthesis process of clopidogrel hydrogen sulfate, selects cheap and easily available materials, adopts mild reaction conditions, and can achieve safe and environment-friendly production of a high-purity product.
Preparation method of sulfonic clopidogrel impurity
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Paragraph 0012; 0037-0038, (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.
Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to Glyoxylates: Access to Optically Active Substituted Mandelic Acid Esters
Chen, Diao,Liu, Jian-Guo,Xu, Ming-Hua,Zhang, Xu
supporting information, p. 1693 - 1697 (2019/08/26)
A rhodium-catalyzed enantioselective addition of glyoxylates to arylboronic acids promoted by a simple chiral sulfinamide-based olefin ligand under mild reaction conditions is described. The reaction provides access to a variety of optically active substituted mandelic acid esters in good yields with up to 83percent ee. The catalytic system is also applicable to pyruvate addition. The synthetic utility of this method is highlighted by a formal synthesis of the antiplatelet drug clopidogrel.
A preparation method of clopidogrel hydrogen sulfate type II
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Paragraph 0114; 0120; 0121; 0154-0158, (2019/07/11)
The invention discloses a preparation method of clopidogrel hydrogen sulfate type II. According to the method, clopidogrel hydrogen sulfate type II is prepared by taking clopidogrel free alkali as a raw material, and a preparation method of clopidogrel free alkali comprises the following steps: (1) preparing a reaction mixed solution of R-chloromandelic acid methyl ester by the reaction of R-chloromandelic acid and methanol in an organic solvent and in the presence of a catalyst; (2) mixing the reaction mixed solution of R-chloromandelic acid methyl ester with an organic base and a catalyst, reacting in the presence of benzenesulfonyl chloride to obtain a reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate; (3) mixing the reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate obtained in the step (2) with 4,5,6,7-Tetrahydrothieno[3,2,c] pyridine hydrochloride and potassium carbonate for reaction to obtain the clopidogrel free alkali. According to the method, the solvent does not need to be supplemented in the last two steps, the solvent is directly used, and the reaction liquid concentration time is saved.
