Abstract: The invention relates to the field of pharmaceutical synthesis, in particular to a preparation method of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivatives and their intermediates. The preparation method is carried out starting from compound Formula A1. In the preparation of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivatives, the chirality was constructed by enzymatic method, and the products were prepared with high optical purity. The preparation method can be used to produce the key intermediates of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol of darunavir commercially, which is a very economical route suitable for industrial production.

Abstract: The invention relates to the field of pharmaceutical synthesis, in particular to the preparation method of hexahydrofuro-furanol derivative, intermediates thereof and preparation methods thereof. The preparation methods comprises the steps of halogenation reaction, acylation reaction, enzymatic reduction reaction, reaction with amine compounds, reduction ring closure reaction (A1, A2, B, Cp1, CL, Cf) wherein, R1, R2, R3 are hydrogen or hydroxy protecting groups; R4 and R5 are the same or different and are phenyl, alkyl or substituted phenyl. In the preparation process of hexahydrofuro-furanol derivatives, the chirality is constructed by enzymatic method, and the product can be prepared with very high optical purity by adopting such technical means. The preparation method can be used to prepare the key intermediate, (3R, 3aS, 6aR)-hexahydrofuro[2,3-b]-3-ol, of Darunavir, in commercial production, which is a very economical route suitable for industrial production.

Abstract: The invention relates to the field of pharmaceutical synthesis, in particular to a preparation method of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivatives and their intermediates. The preparation method is carried out starting from compound Formula A1. In the preparation of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol derivatives, the chirality was constructed by enzymatic method, and the products were prepared with high optical purity. The preparation method can be used to produce the key intermediates of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol of darunavir commercially, which is a very economical route suitable for industrial production.

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.