Purification of Glucuronide Derivatives via Methanol Precipitation
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Solution Overview
Problem
Existing methods for purifying quinolinyl-2-yl-phenylalamine glucuronide derivatives, such as those described in WO 2016/135052, are not compliant with industrial scale production due to difficulties in handling solid extracts and achieving acceptable purity and residual solvent levels.
Innovation Solution
A method involving a solubilization step with methanol followed by precipitation with water, and a drying step at a temperature of 30° C or lower, is developed to purify quinolinyl-2-yl-phenylalamine glucuronide derivatives, allowing for industrial-scale compliance and improved purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If extraction with ethyl acetate followed by concentration to dryness is used to purify crude compound (1), then purification is achieved, but the process is not compliant with industrial scale production due to difficulties in handling solid extracts
Solution Approach 1:
The invention replaces the concentration-to-dryness step with a precipitation step where the purified compound is induced to precipitate from solution as a solid. This phase transition from dissolved state to precipitated solid allows for easy filtration and handling at industrial scale, while maintaining purification quality. The precipitated solid can be directly filtered and washed without requiring concentration to dryness.
2Manufacturing precision
If concentration to dryness is performed after extraction, then solid extract is obtained, but residual solvent amounts exceed ICH level requirements
Solution Approach 1:
The invention uses precipitation instead of concentration to dryness, allowing the compound to be recovered as a precipitated solid that can be filtered and washed. This approach enables more effective removal of residual solvents through washing, ensuring compliance with ICH level requirements while maintaining high purity levels.
Solution Approach 2:
The invention changes the physical state parameters by precipitating the compound from solution rather than concentrating to dryness. By controlling precipitation conditions and followed by washing, the residual solvent content is reduced to meet ICH requirements while maintaining product purity.
3Manufacturing precision
If solid extracts are handled at industrial scale, then purification is completed, but operational difficulties and feasibility issues arise
Solution Approach 1:
The invention performs purification while the compound remains in solution phase, then induces precipitation to obtain the purified solid. This eliminates the need to handle concentrated viscous extracts or dry solids during the purification process, making operations much easier and more feasible at industrial scale. The precipitated solid can be directly filtered and processed.
4Manufacturing precision
If existing purification methods are used, then crude compound (1) is purified, but the process is not adapted for industrial implementation with acceptable yield
Solution Approach 1:
The invention uses precipitation to recover the purified compound as a solid that can be easily filtered and washed. This approach improves productivity at industrial scale by eliminating time-consuming concentration steps and enabling efficient solid-liquid separation through filtration. The process maintains purification effectiveness while being fully adapted for industrial implementation.
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 method achieves high purity levels of the quinolinyl-2-yl-phenylalamine glucuronide derivatives, with residual solvent amounts meeting ICH level requirements, thus addressing the challenges of industrial-scale production.
Implementation Method 1
a solubilization step of said crude compound of formula (I) with methanol
Implementation Method 2
followed by a precipitation step with water
Implementation Method 3
a drying step under a temperature inferior or equal to 30° C.
Data Source
AI summary
A process of purification of a crude compound of formula (I)wherein it includes an isolation step of the crude compound of formula (I) including: (i) a solubilization step of the crude compound of formula (I) with methanol followed by a precipitation step with water, and (ii) a drying step under a temperature inferior or equal to 30° C. Herein is further provided a manufacturing process for preparing a compound of formula (I).