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Overcoming a solid solution system on chiral resolution: combining crystallization and enantioselective dissolution
Ryusei Oketani1, Koki Shiohara1, Ichiro Hisaki1
1Division of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan. r.oketani.es@osaka-u.ac.jp.
Chemical Communications (Cambridge, England)
|April 25, 2023
Summary
Chiral resolution of rac-4-cyano-1-aminoindane, an ozanimod intermediate, was achieved using crystallization and enantioselective dissolution. This method yielded high enantiomeric excess, crucial for pharmaceutical synthesis.
Area of Science:
- Chemical Engineering
- Organic Chemistry
- Pharmaceutical Science
Background:
- Racemic 4-cyano-1-aminoindane is a critical intermediate in the synthesis of ozanimod.
- Efficient chiral resolution methods are essential for producing enantiomerically pure pharmaceutical compounds.
Purpose of the Study:
- To develop and optimize a chiral resolution process for racemic 4-cyano-1-aminoindane.
- To achieve high enantiomeric excess (ee) for this key ozanimod intermediate.
Main Methods:
- Combination of fractional crystallization and enantioselective dissolution.
- Characterization of the diastereomeric salt using binary phase diagrams and ternary isotherms.
Main Results:
- Successful chiral resolution of racemic 4-cyano-1-aminoindane.
- Achieved up to 96% enantiomeric excess (ee).
- Demonstrated the effectiveness of enantioselective dissolution for further enrichment.
Conclusions:
- The developed method provides an efficient route for the chiral resolution of 4-cyano-1-aminoindane.
- The process is suitable for large-scale production of enantiomerically pure intermediates for ozanimod synthesis.
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