Magnesium valproate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of magnesium valproate in absolute ethanol was obtained in the following manner. To a magnetically stirred, clear, colorless solution of valproic acid (31.7 g; 0.22 mol; Sigma Aldrich Chemical Co.) in 200 mL of absolute ethanol was added 11.4 g (0.1 mol) of magnesium ethoxide solid; residual solid was rinsed in with 1 mL of absolute ethanol. Within 30 minutes, a clear, pale yellow solution was obtained; no increase in reaction temperature was observed. Acetonitrile (150 mL) was added to the ethanol solution in portions, and when the addition was complete a white precipitate formed. The reaction mixture was cold to the touch. The slurry was stirred for 15 minutes. The product, magnesium valproate hydrate, was isolated by filtration, washed with fresh acetonitrile, and dried to constant weight. The product, magnesium valproate hydrate, was obtained in 79.8% yield as a white solid, which exhibited an elemental composition identical to that calculated for magnesium valproate hydrate. The product did not melt at temperatures as high as 300° C. The product was not hygroscopic or deliquescent and was stable during storage under ambient conditions. The theoretical valproate content (weight %) of magnesium valproate hydrate is 88.6%; the valproate content found by HPLC analysis was 88.2%. residual solid was rinsed in with 1 mL of absolute ethanol a clear, pale yellow solution was obtained no increase in reaction temperature the addition formed The slurry was stirred for 15 minutes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of magnesium valproate in absolute ethanol was obtained in the following manner. To a magnetically stirred, clear, colorless solution of valproic acid (3.17 g; 0.022 mol; Sigma Aldrich Chemical Co.) in 25 mL of absolute ethanol was added 1.14 g (0.01 mol) of magnesium ethoxide solid; residual solid was rinsed in with 1 mL of absolute ethanol. Within 60 minutes, a clear, pale yellow solution was obtained; no heating was observed. One milliliter portions of the solution were aliquoted into test tubes, and a second solvent or solution was added in portions. The results of the additions are summarized in Table 2. A 15 mL portion of acetonitrile was added to an equal volume of the ethanol solution of magnesium valproate. A white precipitate formed, which was isolated by filtration, washed with a fresh portion of acetonitrile, and dried to constant mass. The product, magnesium valproate hydrate, was obtained in 89% yield as a white solid, which exhibited an elemental composition identical to that calculated for magnesium valproate hydrate. The product did not melt at temperatures as high as 300° C. The product was not hygroscopic or deliquescent. The theoretical valproate content (weight %) of magnesium valproate hydrate is 88.6%; the valproate content found by HPLC analysis was 88.5%. residual solid was rinsed in with 1 mL of absolute ethanol a clear, pale yellow solution was obtained a second solvent or solution was added in portions The results of the additions A white precipitate formed which was isolated by filtration washed with a fresh portion of acetonitrile dried to constant mass

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 11.4 g (0.1 mol) of magnesium ethoxide solid was added to a magnetically stirred, clear, colorless solution of valproic acid (28.8 g; 0.2 mol; Sigma Aldrich Chemical Co.) in 25 mL of absolute ethanol. Residual solid was rinsed into the reaction with 5 mL of absolute ethanol to provide a total volume of 30 mL of absolute ethanol. Within 10 minutes, the slurry became very warm to the touch, and the color of the solution phase changed to pale yellow. Complete dissolution of the magnesium ethoxide solid in ethanol was never achieved, but within minutes the solid phase converted from a slurry of a yellow granular solid to a suspension of white solid that was so thick that stirring stopped. 100 mL of acetone was added, and the thick slurry was stirred for 10 minutes. The precipitate was isolated by filtration, washed with fresh acetone, and dried to constant weight. The product, magnesium valproate, was obtained in 66% yield. Elemental analysis (Table 1) indicated that the product was an inhomogeneous mixture of magnesium valproate and other magnesium salts. The theoretical valproate content (%) of magnesium valproate is 92.2%; the valproate content found by HPLC analysis was 78.4%. Residual solid was rinsed into the reaction with 5 mL of absolute ethanol to provide a total volume of 30 mL of absolute ethanol the slurry became very warm to the touch within minutes the solid phase converted from a slurry of a yellow granular solid to a suspension of white solid that stirring the thick slurry was stirred for 10 minutes The precipitate was isolated by filtration washed with fresh acetone dried to constant weight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Surprisingly, the inventors have discovered that a heretofore unknown valproate salt, magnesium valproate hydrate, a white solid having the molecular formula C16H30O4Mg.x H2O, is recovered in high yields from an alcoholic solution of magnesium valproate by adding a polar, non-oxygen-containing organic solvent having a boiling point of about 130° C. or lower in a volume sufficient to reduce the solubility of the magnesium valproate in the resulting reaction mixture to less than about 0.01 g/mL. The polar, non-oxygen-containing organic solvent is acetonitrile, propionitrile, butyronitrile, or isobutyronitrile. Acetonitrile is most preferred. is recovered