79918-80-2Relevant academic research and scientific papers
A practical, efficient, and atom economic alternative to the Wittig and Horner-Wadsworth-Emmons reactions for the synthesis of (E)-α,β- unsaturated esters from aldehydes
List, Benjamin,Doehring, Arno,Hechavarria Fonseca, Maria T.,Job, Andreas,Rios Torres, Ramon
, p. 476 - 482 (2006)
We describe a highly efficient new methodology for the synthesis of (E)-α,β-unsaturated esters from aldehydes. In our DMAP-catalyzed reaction, both aromatic as well as aliphatic aldehydes furnish the desired products highly regio- and stereoselectively if treated with commercially available or synthetically easily accessible malonic acid half ester. A large scale application in the synthesis of p-methoxycinnamates, which are of use as sunscreen ingredients, is described.
Method for preparing pregabalin by photocatalysis (by machine translation)
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Paragraph 0004, (2020/06/05)
The preparation method is characterized by comprising the 3S following -3 - steps:5 - 1) dissolving the compound I and a certain amount of alkali in an organic solvent, adding the compound II, heating the reaction, obtaining the compound III, 2) preparing the compound V; 3) preparing the compound V through deprotection, ring opening, chiral resolution, and recrystallization to obtain pregabalin. The preparation method comprises the following steps: 1) dissolving compound III, compound IV and photocatalyst in an organic solvent. The raw materials used in the invention are cheap and easily available, the reaction conditions of the photocatalytic oxidation method are mild, reagents are environmentally friendly, green and environment-friendly, and the method is an ideal industrial production process. (by machine translation)
Bisheterocycle substituted oxa-spiro derivative, and preparation method and medical application thereof
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Paragraph 0209; 0397-0399, (2020/09/23)
The invention relates to a bisheterocyclic substituted oxa-spiro derivative, and a preparation method and medical application thereof. Specifically, the invention discloses compounds of formula (I) and formula (II) or pharmaceutically acceptable salts, stereoisomers or solvates thereof, and a preparation method and application thereof. Each group in the formulas is as defined in the specificationand claims in detail.
Synthesis method of pregabalin intermediate 3-nitromethylene-5-methyl-ethyl hexanoate
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Paragraph 0022; 0026; 0027, (2020/02/27)
The invention provides a synthesis method of a pregabalin intermediate, namely 3-nitromethylene-5-methyl-ethyl hexanoate. The synthesis method comprises the following steps: (1) reacting isovaleraldehyde with malonic acid in a choline chloride-urea eutectic solvent to obtain 5-methyl-2-hexenoic acid; (2) reacting the 5-methyl-2-hexenoic acid with absolute ethyl alcohol in a choline chloride-methanesulfonic acid eutectic solvent to obtain 5-methyl-2- ethyl hexanoate; and (3) reacting the 5-methyl-2- ethyl hexanoate with nitromethane in a choline chloride-urea eutectic solvent to obtain the 3-nitromethylene-5-methyl- ethyl hexanoate. The method does not need an organic solvent, is green, low in toxicity, environment-friendly, simple to operate, simple in post-treatment, high in yield and lowin cost, and is a green and efficient synthesis method for synthesizing the pregabalin intermediate.
Method for preparing 3-isobutylglutaric acid
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Page/Page column 6-9, (2019/10/04)
The invention discloses a method for preparing 3-isobutylglutaric acid. The method includes the following steps: carrying out a Knoevenagel condensation reaction on isovaleraldehyde and diethyl malonate with hexahydropyridine acetate as a catalyst in a cyclohexane solvent; carrying out a heating decarboxylation reaction on a product obtained by the first step in a solution composed of sodium chloride, DMSO and water; carrying out a Michael addition and decarboxylation reaction on a product obtained by the second step and diethyl malonate in an alcohol solvent of an alkali; and carrying out a hydrolysis reaction on a product obtained by the third step under an acidic condition to obtain the 3-isobutylglutaric acid product. The method of the invention uses the cheap and easily available isovaleraldehyde and diethyl malonate as raw materials, overcomes the defect of large steric hindrance of carbon-carbon a double bond in 5-methyl-2-cyano-2-hexenoate in the prior art, shortens the reaction time, and increases the reaction conversion rate of the isovaleraldehyde, thereby ensuring the overall yield of the 3-isobutylglutaric acid product.
Synthetic method of environment-friendly and efficient pregabalin
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Paragraph 0071-0082, (2019/02/04)
The invention relates to a synthetic method of environment-friendly and efficient pregabalin. The synthetic method comprises the following steps: 1) dehydrating and condensing acetate and isopentyl aldehyde to obtain 5-methyl-2-hexenoate; 2) performing cyano addition on the 5-methyl-2-hexenoate to obtain (S)-5-methyl-3-cyanohexanoate; 3) performing hydrogen reduction cyclization on the (S)-5-methyl-3-cyanohexanoate to obtain (S)-4-isobutylpyrrolidin-2-one; and 4) performing hydrolysis and ring opening on the (S)-4-isobutylpyrrolidin-2-one to obtain the pregabalin. The synthetic route has the advantages of cheap and easily available raw materials, few reaction steps, mild process conditions, simple operation, high reaction yield and less environment pollution, and is more suitable for industrial production of bulk drug pregabalin.
Phosphodiesterase inhibitor, and applications thereof
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Paragraph 0094-0097, (2018/09/08)
The invention belongs to the technical field of medicine, and more specifically relates to a phosphodiesterase 9 (PDE9) inhibitor represented by formula I, and pharmaceutically acceptable salts, solvates, polymorphic substances, and isomers thereof, and also relates to medicinal preparations, and pharmaceutical compositions of the above compounds, and applications of the medicinal preparations andpharmaceutical compositions. The compounds and the pharmaceutically acceptable salts, solvates, polymorphic substances, and isomers can be used in treatment of phosphodiesterase 9 (PDE9) abnormal expression mediated related diseases.
Evaluation of several routes to advanced pregabalin intermediates: Synthesis and enantioselective enzymatic reduction using ene-reductases
Debarge, Sebastien,McDaid, Paul,O'Neill, Pat,Frahill, James,Wong, John W.,Carr, Donncha,Burrell, Adam,Davies, Simon,Karmilowicz, Mike,Steflik, Jeremy
, p. 109 - 121 (2014/05/20)
This publication describes the evaluation of four synthetic routes to the advanced pregabalin (Lyrica) intermediate 7. Asymmetric reduction of (E)-7 with an ene-reductase (OPR1 from Lycopersicon esculentum) gave a saturated cyanoester intermediate 5 with the desired S stereocenter in ≥99% ee. OPR1 also catalyzed the reduction of (Z)-7 to (S)-5, but with lower conversion and selectivity.
PROCESS FOR PREPARING PREGABALIN
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Page/Page column 6, (2012/06/16)
The invention relates to a process for preparing a compound of formula (I): wherein said process comprises hydrogenation of a compound of formula (II); under alkaline conditions, wherein R represents hydrogen or a labile group capable of being converted to hydrogen. The invention also relates to intermediates used in said process, to the use of said intermediates in the preparation of pregabalin and to a process for resolving racemic compounds of formula (I).
PROCESS FOR THE PREPARATION OF ( S ) - 3 - CYANO - 5 - METHYLHEXANOIC ACID DERIVATIVES ADN OF PREGABALIN
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Page/Page column 20-21, (2012/03/26)
The invention provides a process for the manufacture of a compound of formula (I) using an enzyme catalysed reduction of a compound of formula (lla) or llb). Compounds of formula (I) are useful for preparing pregabalin.
