Calcobutrol Production via Gadobutrol Deprotection and Crystallization
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Solution Overview
Problem
Current methods for producing calcobutrol are not economically viable, complex, and involve the use of toxic or harmful reagents, making it difficult to achieve high purity without resorting to resin purification and deprotection processes.
Innovation Solution
A method involving the reaction of gadobutrol with a decomplexing agent like tartaric acid to obtain butrol, followed by filtration and reaction with calcium ions in the presence of a nano-filter and crystallization using an organic solvent to achieve high purity calcobutrol, excluding resin purification and deprotection steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If conventional methods using butrol as starting material are used, then calcobutrol can be produced, but the purity is insufficient (<95%) and cannot meet preparation requirements
Solution Approach 1:
The invention extracts and removes impurities from the reaction mixture through filtration and centrifugation steps. Specifically, insoluble byproducts and metal salts are separated from the calcobutrol solution through solid-liquid separation techniques, achieving high purity without requiring complex resin purification processes.
Solution Approach 2:
The invention changes physical parameters such as temperature, pH, and solvent composition to optimize purification. By adjusting these parameters, the solubility differences between calcobutrol and impurities are maximized, enabling effective separation through simple filtration and crystallization rather than complex purification processes.
2Manufacturing precision
If resin purification and deprotection processes are used to achieve high purity calcobutrol, then purity >99% can be obtained, but the process becomes complicated and less economical
Solution Approach 1:
The invention extracts and removes impurities from the reaction mixture through filtration and centrifugation steps. Specifically, insoluble byproducts and metal salts are separated from the calcobutrol solution through solid-liquid separation techniques, achieving high purity without requiring complex resin purification processes.
Solution Approach 2:
The invention discards harmful reagents and simplifies the process by eliminating unnecessary steps. Instead of using toxic decomplexing agents followed by complex resin purification and deprotection, the method directly produces high-purity calcobutrol through simplified reaction and filtration steps, recovering only the essential product.
3Productivity
If toxic reagents like oxalic acid or harmful substances like tert-butylbromoacetate are used, then calcobutrol can be manufactured, but safety and environmental issues arise
Solution Approach 1:
The invention replaces expensive and harmful reagents with safer, more environmentally friendly alternatives. Instead of using toxic oxalic acid or harmful tert-butylbromoacetate, the method employs benign reagents that are less harmful to human health and the environment, maintaining manufacturing capability while improving safety.
Solution Approach 2:
The invention converts potentially harmful byproducts into beneficial or harmless substances. The reaction pathway is designed to produce water-soluble byproducts that can be easily removed through filtration and washing, transforming what could be toxic waste into easily manageable materials.
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
This method results in a simpler, more economical, and safer production of calcobutrol with high purity (>99.5%), reducing the use of toxic substances and simplifying the process while maintaining high yield and product quality.
Implementation Method 1
filtration and reaction with calcium ions in the presence of a nano-filter
Implementation Method 2
crystallization using an organic solvent to achieve high purity calcobutrol
Data Source
AI summary
Disclosed is a method for producing calcobutrol used as an MRI contrast agent. The method comprises the steps of: obtaining butrol represented by chemical formula 2 in the specification by reacting a gadobutrol represented by chemical formula 1 in the specification and a decomplexing agent; and obtaining a calcobutrol represented by chemical Formula 3 in the specification by reacting butrol with calcium ions.