Zhejiang Huahai Pharmaceutical Co., Ltd.

Zhejiang Huahai Zhicheng Pharmaceutical Co., Ltd

Zhejiang Huahai Zhicheng Pharmaceutical Co., Ltd. (Cn)

Wenling Zhang

Peng Wang

Pan Guo

Yifeng Wang

Xini Zhang

Jian Chen

Musong Liu

Zhiwen Zeng

Changming Yang

Shudong Wang

Yongbi Chen

Xuehai You

Gang Qian

Lingjie Chen

Zengle Zhou

Linxiang Zhang

Yanbao Zhou

The present invention relates to a method for preparing pregabalin by a biological enzyme method. In particular, the method comprises producing pregabalin B and an R-configuration compound C by using a compound A as a raw material under the action of a biological enzyme; performing configuration inversion of the separated and recovered R-configuration compound C under the action of an isomerase to produce an S-configuration compound D; and producing pregabalin B from the compound D under the action of a biological enzyme.

Method for preparing pregabalin

A method for preparing pregabalin chiral intermediate (R)-3-(carbamoylmethyl)-5-methylhexanoic acid by a biological enzyme method. In particular, the method comprises: reacting compound (I) 3-isobutylglutaric acid, as a raw material, with a nitrogen-containing agent to produce compound (II) 3-isobutylglutarimide; and performing stereoselective ring-opening of compound (II) under the action of a biological enzyme to produce compound (III) (R)-3-(carbamoylmethyl)-5-methylhexanoic acid: 

Method for preparing pregabalin intermediate (R)-3-(carbamoylmethyl)-5-methylhexanoic acid

Disclosed is a method for preparing a canagliflozin form. The method comprises the following steps: adding canagliflozin into an organic solvent and dissolving same, then distilling into a certain amount of an oil; then, adding an anti-solvent to the oil, stirring same with a precipitated solid, cooling, filtering, and drying to obtain the canagliflozin amorphous form. The preparation method has the characteristics of a low solvent ratio, a high yield, a simple operation, easy recovery, less three wastes and good producibility, with the resulting product having a stable quality, good fluidity, and being suitable for the preparation of formulations, etc., and the preparation process is easy to apply to large commercial production, and has a high value in terms of promotion and application.

Method for preparing canagliflozin amorphous form

Provided is a method for preparing a pregabalin intermediate 3-isobutylglutaric acid monoamide. The method comprises: 1) adding 3-isobutylglutaric acid and urea into a first organic solvent; 2) keeping warm and refluxing when heated to 100-140&#xb0; C.; 3) adding water when cooled to 70-90&#xb0; C.; 4) adding an ion membrane alkaline when cooled to 40-60&#xb0; C., adjusting the pH to 11.0-14.0, then keeping warm at 40-60&#xb0; C.; 5) when finished keeping warm, removing an organic layer; 6) adding an acid into the water layer to adjust the pH to 1.0-3.0; 7) extracting the solution acquired in step 6) by using a second organic solvent of a total volume of V, vacuum distilling 0.5-0.6 V of the organic solvent from an organic layer acquired by extraction; and 8) cooling to 0-15&#xb0; C. and crystallizing to acquire 3-isobutylglutaric acid monoamide.

Method for preparing pregabalin intermediate 3-isobutylglutaric acid monoamide

Provided is a purifying method for dabigatran etexilate free base, comprising subjecting a dabigatran etexilate free base crude product to water slurrying to obtain a crude product B; then conducting recrystallization on the crude product B with acetone and water to obtain a crude product C; and subsequently, purifying the crude product C with a mixed solvent of tetrahydrofuran and ethyl acetate, filtering and drying to obtain a dabigatran etexilate free base finished product. The purifying method of the present invention can effectively remove various impurities and is suitable for workshop production. Salts and water-soluble organic impurities are removed by purified water slurrying, impurities with a high polarity are removed by purifying with an acetone-water solution, and impurities with a low polarity are removed by purifying with a mixed solvent of tetrahydrofuran and ethyl acetate.

Preparation process for high-purity dabigatran etexilate

The present invention provides a method for preparing a pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent. The method comprises the following steps: a) cooling an ammonia water system to a certain temperature; b) adding 3-isobutylglutaric anhydride dropwise to the system, then keeping temperature, and reacting; c) after completing the reaction, adding an acid to the system to adjust pH; d) after adjusting pH, cooling, then keeping temperature, crystallizing, then suction filtering and drying; and e) adding a solvent to the dried substance, slurrying, and suction filtering and drying to obtain the final product. The method provided in the present invention for preparing 3-carbamoymethyl-5-methylhexanoic acid is high-yield, green, environmentally-friendly, simple and convenient, and of less pollution.

Method for preparing pregabalin intermediate 3-carbamoymethyl-5-methylhexanoic acid without solvent

The present invention provides a method for recycling 3-carbamoylmethyl-5-methylhexanoic acid from 3-carba carbamoylmethyl moymethyl-5-methylhexanoic acid chiral resolving mother liquor. The method comprises the following steps: (a) distilling 3-carbamoylmethyl-5-methylhexanoic acid chiral resolving mother liquor, adding aromatic hydrocarbon, heating to dissolve, keeping the temperature and stirring; (b) after completing the reaction in step (a), cooling the reaction solution to 30-60&#xb0; C., then adding alkali liquor dropwise, keeping the temperature and reacting; and (c) after completing the reaction in step (b), cooling the reactant to 20-30&#xb0; C., layering, adjusting the pH of the separated water layer to 1 to 2, performing extraction by using an organic solvent, distilling an organic phase under a reduced pressure, and crystallizing at 0&#xb1;5&#xb0; C. to obtain 3-carbamoylmethyl-5-methylhexanoic acid. The method provided in the present invention is convenient to operate, and the recycled product is high in purity (&#x2265;99.8%) and yield.

Method for preparing 3-carbamoymethyl-5-methylhexanoic acid in recycling way

The present invention relates to a method of refining valsartan comprising more than or equal to 10% D-isomers, the method comprising: adding a solvent to valsartan comprising more than or equal to 10% D-isomers to dissolve it, then adding a certain amount of inorganic base, separating solids out after salification, distilling a filtrate after filtration, and distilling the filtrate to remove the organic solvent; adjusting the pH of the filtrate with an acid, extracting with an organic solvent, concentrating most of the organic solvent, cooling to crystallize, and obtaining the product. The method enables isomers of the product to be below 0.5%, and produce a yield of more than or equal to 40%, being suitable for industrial production.

Method of refining valsartan comprising more than or equal to 10% D-isomers

A method for preparing rocuronium is disclosed. 2&#x3b2;-(4-Morpholinyl)-16&#x3b2;-(1-pyrrolidinyl)-5&#x3b1;-androstan-3&#x3b1;-ol-17&#x3b2;-acetate is used as a starting material and is directly reacted with 3-bromopropene at ambient temperature to produce rocuronium.

Preparation method of rocuronium

Provided is a method for purifying rocuronium bromide, which comprises: formulating crude rocuronium bromide to be purified into an aqueous solution, distilling off excess residue solvents at reduced pressure, absorbing by adding active carbon or silica gel, then filtrating, quick freezing the filtrate into ice, and then lyophilizing to obtain rocuronium bromide.

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Taizhou, China

Wenling Zhang