186038-82-4Relevant articles and documents
Preparation method of 1-cyano-3-methylbutyldiethyl malonate
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Paragraph 0060; 0063-0066, (2021/06/12)
The invention provides a preparation method of 1-cyano-3-methylbutyldiethyl malonate (CNDE), and belongs to the technical field of medical technology (organic synthesis). The technical key point is that the preparation method comprises the following steps: (1) carrying out Knoevenagel condensation reaction on isovaleraldehyde, diethyl malonate and a solvent in the presence of catalysts dipropylamine and acetic acid to obtain a CNDE01 product; and (2) adding the CNDE01, sodium cyanide, water and a solvent into a closed kettle, and reacting under the action of carbon dioxide to obtain the CNDE product. The invention aims to provide the preparation method of the 1-cyano-3-methylbutyldiethyl malonate (CNDE), the defects of the existing production process are overcome, and the preparation method has the advantages of low raw material cost, high product purity and yield, few three wastes and the like.
Method for synthesizing Pregabalin by taking isovaleraldehyde as raw material
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, (2016/10/08)
The invention discloses a method for synthesizing Pregabalin by taking isovaleraldehyde as a raw material. The method comprises the steps: carrying out Knoevenagel condensation on isovaleraldehyde and diethyl malonate in a cyclohexane solvent by taking a mixture of di-n-propylamine and acetic acid as a catalyst; carrying out Michael addition on the product obtained in the step one in an alkaline alcohol solvent; carrying out deacidifying reaction on the product obtained in the step two in a solvent prepared from DMSO and water by taking lithium chloride as a catalyst under the condition of heating; carrying out hydrolytic reaction on the product obtained in the step three under alkaline conditions; carrying out catalytic hydrogenation on the product obtained in the step four by taking Raney nickel as a catalyst; and carrying out chiral resolution on the product obtained in the step five by adopting lipase Lipolase 100T. According to the method, isovaleraldehyde, which is cheap and is readily available, serves as a raw material and is subjected to Knoevenagel condensation reaction, Michael addition, decarboxylation, hydrolysis, hydrogenation reaction and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
PROCESS TO PREPARE HIGHLY PURE (S)-PREGABALIN
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Page/Page column 14, (2010/06/17)
A process for the preparation of (S)-pregabalin of formula I containing cyanide ion content less than 5 ppm or free from the cyanide ion,by extracting its cyano diester intermediate of formula III, wherein R11 and R22 are the same or different and are hydrogen, C11-C66 alkyl, aryl, benzyl, substituted benzyl, or C33-C66 cycloalkyl. with an aqueous solution containing a cyanide quenching agent to remove free cyanide ion from the reaction mixture.