181289-15-6Relevant articles and documents
Development of a new synthesis approach for S-pregabalin by optimizing the preparation stages
Mansoori, Arsalan,Zahednezhad, Fahimeh,Bavili Tabrizi, Ahad,Shahbazi Mojarrad, Javid
, p. 89 - 101 (2019/09/13)
In the present study, we aimed to optimize the synthesis stages of S-pregabalin ((S)-3-(aminomethyl)-5-methylhexanoic acid), a well-known anticonvulsant drug. We used appropriate solvents and compounds to reach a straightforward and applicable method. The advantages of this research were avoiding use of expensive and environment pollutant reagents and solvents, and also using a recoverable reagent. Discarding prevention of the intermediates and reagents besides attaining a higher yield of the obtained product were the additional achievements. All structures were characterized by FT-IR, 1H NMR, and the purity of S-pregabalin was evaluated using the HPLC assay.
Pregregregabalin intermediate mother liquor and method for recycling wastewater
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Paragraph 0032-0049, (2020/09/23)
The invention provides a preparation method for mechanically applying Pregabalin 3-isobutyl-glutarate monoamide intermediate mother liquid and waste water. The method comprises the following steps: (1) dropwise adding 3-isobutyl glutaric anhydride into stronger ammonia water with the mass fraction of 25-28%, and carrying out insulation reaction; (2) adding reclaimed waste water into the system, and then dropwise adding acid slowly into the system to adjust the pH value to be 2.0-3.0; (3) adding the mother liquid into the system, extracting with an organic solvent for layering, and then carrying out reduced pressure distillation on an organic layer; and (4) cooling to 5-15 DEG C within 2-3 hours, crystallizing, insulating for 1.5-2 hours, carrying out suction filtration, preserving suction filtration mother liquid, and baking filter cakes, thereby obtaining the target product 3-isobutyl-glutarate monoamide. The method provided by the invention has the advantages that the operation is simple, and the ammonolysis yield is effectively improved; before the ammonolysis mother liquid is mechanically applied, the yield is generally 70-85%; and after the ammonolysis mother liquid is mechanically applied, the yield can reach 99.0-102.0%, so that the productivity is effectively enlarged, and the cost of industrial production is lowered.
Pregabalin intermittent synthesis method
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Paragraph 0014; 0020; 0021, (2019/02/21)
The invention discloses a pregabalin intermittent synthesis method. The method comprises the following step of (1) preparation of 2-cyano-5-methyl-2-hexenyl ethyl ester (A), wherein 94.6 g (1.1mol) ofisovaleraldehyde, 113 g (1.0 mol) of ethyl cyanoacetate, 127 ml of n-hexane and 1.00 g (0.01mol) of di-n-propylamine are put into a 1000 ml reaction bottle in sequence, heating is conducted, reflux reaction is carried out, a water separator is used for water separation, the reaction is carried out until no moisture is separated out, and cooling is conducted. Compared with the prior art, the pregabalin intermittent synthesis method has the following advantages that when methyl tertiary butyl ether is used as a solvent, layering is hard, impurities cannot be removed, the solvent cannot be recycled, the raw material cost is improved, and the amide is low, so that the methyl tertiary butyl ether is not suitable for being used as the solvent; ethyl acetate can be used, however, the intersolubility of the ethyl acetate and water is large, thus a small amount of amide crude product is dissolved in the water, the amide yield is low, meanwhile, the ethyl acetate recovery is low, and by using methylbenzene, the defects of the ethyl acetate are avoided, so that the methylbenzene is selected as an ammoniation solvent. There are no corresponding HPLC standards of the quality situation of amide, however, the quality of the amide obtained by adopting a technology is qualified in later detection.
