Mildronate synthesis

Yield:76144-81-5 95%

Reaction Conditions:

Stage #1:methyl 3-(2,2,2-trimethylhydrazinium)propionate chloride with ethanol;sodium hydroxide at 18 - 20;
Stage #2: with carbon dioxide; pH=8.1 - 8.5Product distribution / selectivity;

Steps:

5
Example 5; 24 g of NaOH were suspended in 450 ml of ethanol and, at 18-20° C., 136 g of methyl-3-(2,2,2-trimethylhydrazinium)propionate chloride during 5-10 min were added under stirring. The stirring was continued at 18-20° C. until ester saponification was completed (controlled by TLC). The mixture was then cooled to 2-4° C. and saturated with CO₂ to pH 8.1-8.5. Precipitate thus formed was filtered off, washed with 3×10 ml of ethanol and the combined filtrates were evaporated. 91 g (95%) of semi-crystalline solid were obtained (3-(2,2,2-trimethylhydrazinium)propionate content 95%). Crystallization from ethanol or propanol-2 or another appropriate solvent gave 3-(2,2,2-trimethylhydrazinium)propionate dihydrate with m.p. 85-87° C. (purity >99.5%).

References:

Silva, Jorge US2009/318731, 2009, A1 Location in patent:Page/Page column 3

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