Strontium Ranelate Synthesis Yield via Water-Organic Solvent
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Solution Overview
Problem
Existing methods for synthesizing strontium ranelate result in low yields, typically less than 70%, which is suboptimal for industrial production.
Innovation Solution
A process involving the reaction of a compound of formula (II) with sodium or potassium hydroxide in the presence of an organic solvent, followed by reaction with strontium chloride, significantly increases the yield of strontium ranelate by using a mixture of water and an organic solvent at controlled temperatures, with optional steps of isolation and clarification.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the second method from EP 0415 850 is used (reflux with soda in hydroalcoholic medium, then reaction with strontium chloride), then the synthesis process can be completed, but the yield of strontium ranelate is less than 70%
Solution Approach 1:
The invention changes the reaction parameters by using a mixture of water and organic solvent (acetone, tetrahydrofuran, or isopropanol) instead of purely hydroalcoholic medium, and by controlling the temperature between 0-100°C during saponification and 0-50°C during salt formation. This optimization of reaction parameters increases the yield from less than 70% to over 90%.
Solution Approach 2:
The invention uses a composite solvent system combining water with organic solvents (acetone, tetrahydrofuran, or isopropanol) in specific proportions. This composite medium improves both the saponification efficiency and the subsequent salt formation reaction, leading to significantly higher yields of strontium ranelate.
2Manufacturing precision
If existing synthesis methods are used, then the process can be implemented, but the purity and efficiency are suboptimal for industrial production
Solution Approach 1:
The invention performs preliminary saponification of the ethyl tetraester to obtain the disodium salt intermediate, which is then used in the salt formation step. This preliminary action ensures complete hydrolysis before salt formation, improving both purity and efficiency of the final product.
Solution Approach 2:
The disodium salt of 5-[bis(carboxymethyl)amino]-3-carboxymethyl-4-cyano-2-thiophenecarboxylic acid serves as an intermediary compound that facilitates the transformation from the ethyl tetraester to strontium ranelate. This intermediate step allows for better control over the reaction process and improved product quality.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The process achieves high yields of strontium ranelate, up to 94.8%, with improved purity and efficiency, utilizing organic solvents like tetrahydrofuran, acetone, or isopropanol, and optimizing reaction conditions such as temperature and stoichiometry.
Implementation Method 1
a compound of formula (II) which is reacted with sodium hydroxide or potassium hydroxide, in the water or in a mixture of water and an organic solvent, at a temperature between 0 and 100° C., to yield the salt of formula (III)
Implementation Method 2
the salt of formula (III) is reacted with strontium chloride, in a mixture of water and an organic solvent, at a temperature between 0 and 100° C., to lead after isolation to strontium ranelate
Data Source
AI summary
Synthesizing strontium ranelate compounds (I) and their hydrates, comprises: reacting 3-cyano thiophene compound (II) with soda or potash, in water or mixture of water and organic solvent at 0-100[deg] C, to give a salt of 5-(bis-carboxymethyl-amino)-3-carboxymethyl-4-cyano-thiophene-2-carboxylic acid (III); and reacting strontium chloride with mixture of water and organic solvent at 0-100[deg] C to give (I), after the isolation. Process for synthesizing strontium ranelate compounds of formula (I) and its hydrates, comprises: reacting 3-cyano thiophene compound of formula (II) with soda or potash, in water or mixture of water and organic solvent at 0-100[deg] C, to give a salt of 5-(bis-carboxymethyl-amino)-3-carboxymethyl-4-cyano-thiophene-2-carboxylic acid of formula (III); and reacting strontium chloride with mixture of water and organic solvent at 0-100[deg] C to give (I), after the isolation. R, R1 : 1-6C alkyl, preferably CH 3; and A : Na or K. An independent claim is included for a potassium salt of 5-(bis-carboxymethyl-amino)-3-carboxymethyl-4-cyano-thiophene-2-carboxylic acid of formula (IIIb). [Image] [Image] [Image] ACTIVITY : Osteopathic. MECHANISM OF ACTION : None given.