40412-06-4Relevant academic research and scientific papers
Preparation method of clopidogrel hydrogen sulfate intermediate
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Paragraph 0032, (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.
Preparation method of sulfonic clopidogrel impurity
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Paragraph 0012; 0024-0026, (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.
The clopidogrel hydrogen sulfate synthesis method (by machine translation)
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Paragraph 0006; 0008, (2018/11/22)
The invention discloses a clopidogrel hydrogen sulfate synthesis method, comprises the following steps: S1, 2 - (2 - thiophene) ethanol tosylates synthetic, S2, (+) - O-chlorobenzene glycine methyl brown oil of synthetic, S3, (S)- 2 - (2 - thiophene ethylamine) (2 - chlorophenyl) acetic acid methyl ester hydrochloride of synthetic, S4, the finished synthetic; the invention with conventional clopidogrel hydrogen sulfate existing synthesis method, the processing operation is more convenient, after treatment is simple, and is suitable for commercial production; high yield, few by-products, impurity removal easier; simple and easy to obtain, the cost is cheap. (by machine translation)
Method for preparing D-(+)-alpha-(2-thiopheneethylamino)-alpha-(2-chlorophenyl)methyl acetate hydrochloride
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Paragraph 0009; 0058; 0064; 0067; 0076; 0083; 0094; 0103, (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.
Structure-Odor Correlations in Homologous Series of Mercapto Furans and Mercapto Thiophenes Synthesized by Changing the Structural Motifs of the Key Coffee Odorant Furan-2-ylmethanethiol
Schoenauer, Sebastian,Schieberle, Peter
, p. 4189 - 4199 (2018/05/01)
Furan-2-ylmethanethiol (2-furfurylthiol; 2-FFT, 1) is long-known as a key odorant in roast and ground coffee and was also previously identified in a wide range of thermally treated foods such as meat, bread, and roasted sesame seeds. Its unique coffee-like odor quality elicited at very low concentrations, and the fact that only a very few compounds showing a similar structure have previously been described in foods make 1 a suitable candidate for structure-odor activity studies. To gain insight into the structural features needed to evoke a coffee-like odor at low concentrations, 46 heterocyclic mercaptans and thio ethers were synthesized, 32 of them for the first time, and their odor qualities and odor thresholds were determined. A movement of the mercapto group to the 3-position kept the coffee-like aroma but led to an increase in odor threshold. A separation of the thiol group from the furan ring by an elongation of the carbon side chain caused a loss of the coffee-like odor and also led to an increase in odor thresholds, especially for ω-(furan-2-yl)alkane-1-thiols with six or seven carbon atoms in the side chain. A displacement of the furan ring by a thiophene ring had no significant influence on the odor properties of most of the compounds studied, but the newly synthesized longer-chain 1-(furan-2-yl)- and 1-(thiophene-2-yl)alkane-1-thiols elicited interesting passion fruit-like scents. In total, only 4 out of the 46 compounds also showed a coffee-like odor quality like 1, but none showed a lower odor threshold. Besides the odor attributes, also retention indices, mass spectra, and NMR data of the synthesized compounds were elaborated, which are helpful in possible future identification of these compounds in trace levels in foods or other materials.
Synthetic method of p-toluene sulfonic acid-2-thiophene ethyl ester
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Paragraph 0011; 0012, (2017/07/22)
The invention relates to a synthetic method of p-toluene sulfonic acid-2-thiophene ethyl ester. According to the synthetic method, the p-toluene sulfonic acid-2-thiophene ethyl ester is synthesized by using 2-thiopheneethanol and p-toluene sulfonic acid as raw materials and using ferric nitrate as a catalyst through a one-step reaction. The invention provides a new method for synthesizing the p-toluene sulfonic acid-2-thiophene ethyl ester. The method has the characteristics of low cost, environmental-friendliness and simple process, and has industrial application value.
Synthesis method of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride
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Paragraph 0016, (2017/09/02)
The invention relates to a synthesis method of 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride. The method comprises the following steps: synthesizing 2-(2-thienyl)ethyl p-toluenesulfonate from 2-thiopheneethanol and paratoluensulfonyl chloride, further reacting the 2-(2-thienyl)ethyl p-toluenesulfonate with formamide to synthesize N-2-thienylethylformamide, carrying out cyclization on the N-2-thienylethylformamide under the action of trifluoroacetic acid to produce 6,7-dihydrothieno[3,2-c]pyridine, reducing the 6,7-dihydrothieno[3,2-c]pyridine with sodium borohydride, and carrying out salification to obtain the 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride. The invention provides a novel method for synthesizing the 4,5,6,7-tetrahydrothieno[3,2-c]pyridine hydrochloride. The method has the characteristics of low cost, low toxicity and simple technique, and has industrialized application prospects.
A compound clopidogrel hydrogensulfate method for the preparation of
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Paragraph 0094-0096, (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.
A 1,2-bis (2-thienyl) ethane method for the synthesis of
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Paragraph 0015; 0016, (2017/02/09)
The invention relates to a synthesis method of 1,2-di(2-thienyl)ethane, and particularly relates to a synthesis method of 1,2-di(2-thienyl)ethane by firstly converting 2-penphene as a raw material into thienyl borane, then reacting with p-toluene sulfonate-2-(2-thienyl)ethyl to generate 1,2--di(2-thienyl)ethane. The 1,2-di(2-thienyl)ethane is synthesized by the following steps: by taking 2-penphene as a raw material, firstly converting into thienyl borane, then reacting with p-toluene sulfonate-2-(2-thienyl)ethyl to generate 1,2--di(2-thienyl)ethane. The invention provides a new method for synthesizing 1,2-di(2-thienyl)ethane, and the synthesis method has the characteristics of being mild in reaction conditions, short in reaction route, and high in reaction yield.
Method for synthesizing ticlopidine hydrochloride
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Paragraph 0017, (2016/10/17)
The invention provides a method for synthesizing ticlopidine hydrochloride. The method comprises the following steps: by using thiopheneethanol as a raw material, under the action of an acid binding agent, firstly, performing a reaction on the thiopheneethanol and paratoluensulfonyl chloride to carry out protection and activation on hydroxy; performing a condensation reaction with chlorobenzylamine; then under an acid condition, performing a ring closing reaction with 1,3-dioxolane to obtain the ticlopidine hydrochloride. The method is mild in reaction condition, low in production cost, high in product yield and high in quality, and is convenient for industrial production.
