Ozanimod Synthesis via Two-Phase Solvent Extraction
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Solution Overview
Problem
The existing process for preparing ozanimod involves tedious and expensive chromatographic purification steps, which are not feasible on an industrial scale, necessitating an alternative method that achieves sufficient purity and yield without chromatographic purification.
Innovation Solution
A process involving a series of reactions, including reacting a compound with a leaving group in the presence of a base, followed by hydroxylamine and a coupling agent, and finally with a silane compound, to produce ozanimod without the need for chromatographic purification, using a two-phase solvent system to improve yield and purity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If chromatographic purification steps are used to purify intermediates, then purity of intermediates is improved, but process complexity and cost increase significantly
Solution Approach 1:
The invention extracts and eliminates the chromatographic purification steps from the synthesis process. By redesigning the reaction pathway and selecting appropriate reaction conditions, the process achieves sufficient intermediate purity through simple filtration and washing operations, removing the complex chromatography equipment and procedures entirely
Solution Approach 2:
The invention changes key reaction parameters including solvent selection (using ethyl acetate and heptane), temperature control (0-5°C), and reaction sequence to optimize the synthesis. These parameter changes enable the reaction to proceed with high selectivity, producing intermediates with sufficient purity without requiring chromatographic separation
2Manufacturing precision
If chromatographic purification steps are used to purify intermediates, then purity of intermediates is improved, but production cost increases
Solution Approach 1:
The invention replaces expensive chromatographic materials (silica gel, solvents for chromatography) with inexpensive, readily available materials such as ethyl acetate, heptane, and common inorganic salts. These cheap reagents effectively purify intermediates through simple extraction and filtration, dramatically reducing production costs while maintaining adequate purity
Solution Approach 2:
The invention extracts and eliminates the costly chromatographic purification steps from the synthesis process. By redesigning the reaction pathway and selecting appropriate reaction conditions, the process achieves sufficient intermediate purity through simple filtration and washing operations, removing the expensive chromatography equipment and procedures entirely
3Manufacturing precision
If chromatographic purification steps are used to purify intermediates, then purity of intermediates is improved, but production time increases
Solution Approach 1:
The invention extracts and eliminates the time-consuming chromatographic purification steps from the synthesis process. By redesigning the reaction pathway and selecting appropriate reaction conditions, the process achieves sufficient intermediate purity through simple filtration and washing operations, dramatically reducing production time while maintaining adequate purity
Solution Approach 2:
The invention performs preliminary optimization of reaction conditions (solvent selection, temperature control, stoichiometry) to ensure that intermediates are formed with high selectivity and minimal impurities from the start. This preliminary action prevents the formation of difficult-to-remove byproducts, eliminating the need for time-consuming purification steps later in the process
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 process allows for the production of ozanimod in high purity and yield without the need for chromatographic purification, simplifying the industrial-scale production and reducing costs.
Implementation Method 1
Reacting a compound (2) or a salt thereof with compound (3), LG is a leaving group independently selected from Cl or Br or I or an ester selected from methoxy or ethoxy or tosylate or mesylate or benzenesulfonate or triflate in a solvent in a presence of a base
Implementation Method 2
Reacting compound (4) with hydroxylamine or a salt thereof in a solvent to provide compound (5)
Implementation Method 3
Reacting compound (5) with compound (6) in a presence of coupling agent in a solvent to provide compound (7)
Implementation Method 4
Reacting compound (7) in a presence of a compound of formula (R) 3 SiOM, R is selected from R 1 -R 5 alkyl or aryl and M is selected from Na or K or Li in a solvent to provide compound (1)
Data Source
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AI summary
The presented invention relates to a process for preparation of compound of formula (1) or a salt thereof (i.e.) ozanimod : (1). The invention also relates to intermediates used in the process.