Study On Synthetic Processes Of Strontium Ranelate

Strontium ranelate is a kind of anti osteoporosis drug developed by Servier French. It not only cures female postmenopausal osteoporosis but also improves the syndrome of male osteoporosis.The chemical name of strontium ranelate is distrontium salt of5-[N,N-di(carboxy-methyl)amino]-4-cyano-3-carboxymethylthiophene-2-carboxylic acid. Comparing with other anti osteoporosis drugs, strontium ranelate has been proved a dual effect, inhibiting bone resorption and improving bone formation. There is a broad market prospect for strontium ranelate because of this advantage.Studying the published processes, citric acid was chosen to be the start material. Citric acid was reacted in concentrated sulfuric acid to product acetonedicarboxylic acid. Methyl tetraester of ranelic acid was produced from acetonedicarboxylic acid by esterification reaction, cyclization reaction and alkylation reaction. Finally, strontium ranelate was synthesized from methyl tetraester of ranelic acid by hydrolysis reaction and salt formation. Orthogonal experiments and single factor experiments were developed to determine the optimal conditions, and the yield of the process is42.6%. All compounds were confirmed by ’H NMR, MS, elemental analysis and XRD.Comparing with published processes, some reaction conditions and reagents were used to make the process more economical and more environmental. Concentrated sulfuric acid replaced fuming sulphuric acid or chlorosulfonic acid in the decarboxylation reaction to reduce risks and environmental pollutions during the operation. Alkylating agent used in alkylation reaction was methyl chloroacetate so that cost was reduced. The process of cyclization reaction was optimized by orthogonal experiments and single factor experiments to improve yield. Comparing with published processes, the present process has a huge potential in industry.