Abstract: 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° C.; 3) adding water when cooled to 70-90° C.; 4) adding an ion membrane alkaline when cooled to 40-60° C., adjusting the pH to 11.0-14.0, then keeping warm at 40-60° 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° C. and crystallizing to acquire 3-isobutylglutaric acid monoamide.

Abstract: 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° C.; 3) adding water when cooled to 70-90° C.; 4) adding an ion membrane alkaline when cooled to 40-60° C., adjusting the pH to 11.0-14.0, then keeping warm at 40-60° 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° C. and crystallizing to acquire 3-isobutylglutaric acid monoamide.

Abstract: 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.

Abstract: 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.