94188-84-8

Upstream product

• 50-00-0 formaldehyd 
• 141109-18-4 (+)-α-[(2-thien-2-yl)-ethylamino]-α-(2-chlorophenyl)methylacetate hydrochloride 
• 40412-06-4 2-(2-thienyl)ethyl tosylate 
• 213018-92-9 (S)-methyl 2-amino-2-(2-chlorophenyl)acetate hydrochloride salt 
• 61380-07-2 2-(thiophen-2-yl)ethyl methanesulfonate 
• 90055-47-3 methyl 2-chloro-2-(2-chlorophenyl)acetate 
• 54903-50-3 4,5,6,7-tetrahydrothieno[3,2-c]pyridine 
• 67-56-1 methanol 
• 444728-13-6 (+)-α-(4,5,6,7-tetrahydrothieno[3,2-c]-5-pyridyl)-α-2-chlorophenylacetamide 
• 77-78-1 dimethyl sulfate 
• 865187-86-6 6,7-dihydro-4H-thieno[3,2-c]pyran 
• 865187-82-2 2-(2-bromoethyl)-3-(bromomethyl)thiophene 
• 141109-14-0 methyl (S)-(+)-2-amino-2-(2-chlorophenyl)acetate 
• 35963-20-3 (R)-10-camphorsulfonic acid 

Downstream Products

• 1093351-62-2 C₁₆H₁₄⁽²⁾H₂ClNO₂S 
• 144457-28-3 SR 26334 
• 1351983-68-0 C₁₆H₁₈ClNO₄S 
• 767612-34-0 R-361015 

Relevant academic research and scientific papers

Copper (II) bromide catalysed one pot bromination and amination for the green, cost-effective synthesis of clopidogrel

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.

Iridium and bis(4-nitrophenyl)phosphoric acid catalysed amination of diol by hydrogen-borrowing methodology for the synthesis of cyclic amine: Synthesis of clopidogrel

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.

Preparation method of clopidogrel hydrogen sulfate and intermediate N-(2-thiopheneethyl) methyleneimine of clopidogrel hydrogen sulfate

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.

Method for recycling S - O-chloromandelic acid

The invention belongs to the technical field of chemical synthesis, and discloses a method for recycling S-o-chloromandelic acid. The o-chloromandelic acid is a clopidogrel hydrogen sulfate starting material. The method is characterized by comprising the following steps: concentrating a lipid solution of S-o-chloromandelic acid to dryness, and adding an alkaline aqueous solution to react at a hightemperature to racemize the S-o-chloromandelic acid; after the reaction is completed, adding a C2-C8 lipid solvent and adjusting the pH of the solution with an inorganic acid to be acidic; separatingan aqueous phase from an organic phase, and allowing the organic phase to be dried and directly reacted with a resolving agent to prepare R-o-chloromandelic acid. The invention provides a method forrecycling clopidogrel hydrogen sulfate intermediate waste, the influence of reaction byproducts on the environment is eliminated, the S-o-chloromandelic acid is converted and then used in the preparation process of clopidogrel hydrogen sulfate, and the economic value is very high.

Synthetic method of racemic clopidogrel

The invention relates to a synthesis method of racemic clopidogrel, which comprises the following steps: 1) uniformly mixing methyl benzoylformate, N-chlorosuccinimide, palladium acetate, a ligand andtrifluoroacetic acid, and carrying out ortho-chlorinati

Preparation method of sulfonic clopidogrel impurity

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.

Preparation method of clopidogrel hydrogen sulfate crystal form II

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.

Synthetic hydrosulfuric acid clopidogrel and intermediate of the new method (by machine translation)

The invention relates to a synthesis of the clopidogrel hydrogen sulfate of the new method, through 2 - thiophene ethylamine and N - benzyl - 2 - (2 - chlorophenyl) - 2 - carbonyl acetamide generate condensation reaction, generating imine; imine asymmetric hydrogenation reaction is reduced to the corresponding secondary amine. Under acidic conditions, secondary amine with formaldehyde generating ring, get the clopidogrel free base, then acidified by sulfuric acid, to obtain the clopidogrel hydrogen sulfate. The present invention provides a synthetic route of the short, relates to the reaction are classical organic chemical reaction, mild reaction conditions, the operation is simple, with high enantio-selectivity, high yield, high turn over number of characteristics, the vast majority of the substrate in the thousandths of a dosage of the catalyst obtained in the circumstances of 99% or more of the conversion and 97% -99% ee value of, to achieve the highest transformed number 100000, has extremely high industrial application value. (by machine translation)

Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to Glyoxylates: Access to Optically Active Substituted Mandelic Acid Esters

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

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.