Aspects of the disclosure includes methods for preparing an amorphous solid composition of a fatty acid metal salt. In practicing the subject methods according to certain embodiments, a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane organic salt is contacted with a metal base to produce a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt; and the succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt is precipitated in a solvent to produce an amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt composition. An amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane lithium salt is also provided.

Aspects of the disclosure includes methods for preparing an amorphous solid composition of a fatty acid metal salt. In practicing the subject methods according to certain embodiments, a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane organic salt is contacted with a metal base to produce a succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt; and the succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt is precipitated in a solvent to produce an amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane metal salt composition. An amorphous solid succinylated 3-(fatty acid amido)-2-hydroxy-1-(protected hydroxy)-propane lithium salt is also provided.

This application relates to pharmaceutical engineering, and more particularly to a continuous-flow preparation method of diclofenac sodium. The continuous-flow preparation method includes: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide (3); subjecting 2-chloro-N-phenylacetamide (3) and 2,6-dichlorophenol to continuous condensation to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5); subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5) and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6); subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6) to Friedel-Crafts alkylation in the presence of aluminum chloride to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indo1-2-one (7); and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7) to hydrolysis to obtain the diclofenac sodium.

This application relates to pharmaceutical engineering, and more particularly to a continuous-flow preparation method of diclofenac sodium. The continuous-flow preparation method includes: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide (3); subjecting 2-chloro-N-phenylacetamide (3) and 2,6-dichlorophenol to continuous condensation to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5); subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5) and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6); subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6) to Friedel-Crafts alkylation in the presence of aluminum chloride to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indo1-2-one (7); and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7) to hydrolysis to obtain the diclofenac sodium.

The present invention relates to a novel process for preparing cis-alkoxy-substituted spirocyclic phenylacetylamino acid esters and cis-alkoxy-substituted spirocyclic 1H-pyrrolidine-2,4-dione derivatives, and also to novel intermediates and starting materials which are produced and/or used in the process according to the invention.

The present invention relates to a novel process for preparing cis-alkoxy-substituted spirocyclic phenylacetylamino acid esters and cis-alkoxy-substituted spirocyclic 1H-pyrrolidine-2,4-dione derivatives, and also to novel intermediates and starting materials which are produced and/or used in the process according to the invention.

The present invention relates to a novel process for preparing cis-alkoxy-substituted spirocyclic phenylacetylamino acid esters and cis-alkoxy-substituted spirocyclic 1H-pyrrolidine-2,4-dione derivatives, and also to novel intermediates and starting materials which are produced and/or used in the process according to the invention.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of α-hydroxyisobutyramide (HIBAM), α-sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises:—at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, . . . 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall,—said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion,—said compartment being connected to an outlet valve (204a, 204b, . . . 204i). Such vessel allows obtaining a high yield thermal conversion in very safe conditions.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of α-hydroxyisobutyramide (HIBAM), α-sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises:—at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, . . . 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall,—said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion,—said compartment being connected to an outlet valve (204a, 204b, . . . 204i). Such vessel allows obtaining a high yield thermal conversion in very safe conditions.

The invention relates to a thermal conversion vessel (200) used during amidification step of acetone cyanohydrin (ACH), in the industrial process for production of a methyl methacrylate (MMA) or methacrylic acid (MAA). The thermal conversion vessel (200) is used for converting an hydrolysis mixture of α-hydroxyisobutyramide (HIBAM), α-sulfatoisobutyramide (SIBAM), 2-methacrylamide (MACRYDE) and methacrylique acid (MAA), into a mixture of 2-methacrylamide (MACRYDE). It comprises:—at least one compartment (C1, C2, C3, . . . Ci) comprising an inner wall (206a, 206b, . . . 206i) separating said compartment into two communicating parts (C1a, C1b) by a passage provided between the bottom of said vessel and said inner wall,—said compartment having a space above said inner wall, for separating gas phase from liquid phase during thermal conversion,—said compartment being connected to an outlet valve (204a, 204b, . . . 204i). Such vessel allows obtaining a high yield thermal conversion in very safe conditions.