Chiral Salt Resolution for High-Purity (S)-Finerenone
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing processes for the preparation of Finerenone, particularly the (S)-enantiomer, face challenges in achieving high yields and purity, especially at an industrial scale.
Innovation Solution
A process involving chiral resolution with Di-p-toluoyl-D-tartaric acid or Di-benzoyl-L-tartaric acid is used to prepare (S)-Finerenone, utilizing specific solvents and conditions to achieve high enantiomeric excess, followed by conversion to Finerenone through ammonolysis or stereoselective hydrogenation with a chiral catalyst.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chiral chromatography is used for resolution of Finerenone, then enantiomeric purity is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent uses chiral tartaric acid derivatives as resolving agents (intermediaries) to form diastereomeric salts with the racemic Finerenone intermediate. These diastereomeric salts have different solubilities and can be separated by conventional crystallization methods, avoiding the need for complex chiral chromatography while achieving high enantiomeric purity
Solution Approach 2:
The patent changes the physical-chemical parameters of the resolution process by using solvent systems and temperature conditions that exploit the differential solubility of diastereomeric salts. This allows separation through simple filtration and crystallization rather than complex chromatographic techniques
2Manufacturing precision
If conventional chiral resolution methods are used, then enantiomeric excess is improved, but process time and productivity are reduced
Solution Approach 1:
The resolution process is designed to be self-service through spontaneous crystallization of the desired enantiomer's diastereomeric salt from the reaction mixture. The process automatically separates the enantiomers without requiring time-consuming chromatographic elution or multiple purification steps, achieving both high ee and fast throughput
Solution Approach 2:
The patent performs preliminary action by forming the diastereomeric salt complex in situ before any separation step. This pre-organization of the separation system allows direct filtration and isolation of the pure enantiomer, eliminating lengthy chromatographic procedures and significantly reducing overall process time
3Manufacturing precision
If multiple purification steps are implemented, then product purity is improved, but yield and productivity decrease
Solution Approach 1:
The patent takes out the impurities and unwanted enantiomer in the form of the opposite diastereomeric salt, which remains in the mother liquor during crystallization. This single extraction-like separation step achieves both high purity and high yield by eliminating the need for multiple sequential purifications that would otherwise be required
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 (S)-Finerenone with high yields and purity, suitable for large-scale production, using intermediates that can be purified effectively in various solvents to enhance product quality.
Implementation Method 1
chiral resolution of a compound of formula II with a chiral acid selected from Di-p-toluoyl-D-tartaric acid or Di-benzoyl-L-tartaric acid
Implementation Method 2
stereoselective hydrogenation with a chiral catalyst
Data Source
AI summary
The present disclosure encompasses processes for the preparation of (S)-Finerenone.