Chiral 2-Aryl Morpholine Synthesis via Enzymatic Reduction
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Solution Overview
Problem
Current methods for producing chiral 2-(4-aminophenyl) morpholines are not scalable for technical applications, limiting their use in synthesizing compounds with affinity to trace amine associated receptors (TAARs) effectively.
Innovation Solution
A novel process involving enzymatic reduction of ketones using oxidoreductase enzymes, followed by intramolecular displacement, ring opening, and subsequent cyclization, allows for the scalable production of chiral 2-(4-aminophenyl) morpholines, enabling the synthesis of compounds with specific aromatic substituents and their pharmaceutically suitable salts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current methods are used for producing chiral 2-(4-aminophenyl) morpholines, then the production can be performed, but the process is not scalable for technical applications
Solution Approach 1:
The patent replaces conventional chemical reduction methods with enzymatic reduction using oxidoreductase enzymes. This biological catalysis system enables scalable production while maintaining ease of manufacture, as the enzymatic process can be performed under mild conditions with high selectivity and can be readily scaled up for technical applications.
2Manufacturing precision
If conventional synthesis methods are used, then the process is simple, but the enantiomeric excess is insufficient
Solution Approach 1:
The patent introduces oxidoreductase enzymes as intermediary catalysts that mediate the reduction of ketone intermediates to chiral 2-(4-aminophenyl) morpholines. These enzymes provide high enantiomeric excess (>98%) by selectively catalyzing the formation of one enantiomer, while the overall process remains relatively simple involving standard enzymatic reaction conditions and workup procedures.
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 achieves high enantiomeric excess (>98%) and scalability, facilitating the production of compounds with good affinity to TAARs, thereby addressing the limitations of existing methods.
Implementation Method 1
reducing a ketone of the formula II wherein X is a halogen atom with an oxidoreductase enzyme to afford the chiral alcohol of the formula IIIa
Data Source
AI summary
The invention relates to a novel process for the preparation of chiral 2-(4-aminophenyl) morpholines of the formulawherein R1 is hydrogen an amino protecting group.The chiral 2-(4-aminophenyl) morpholines of the formula I are key intermediates for the preparation of compounds that have a good affinity to the trace amine associated receptors (TAARs).