The Synthetic Routes of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine

Synthetic routes of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine: A Comprehensive Review

Introduction:

In the field of organic synthesis, the design and synthesis of novel molecules with desired properties is of utmost importance.
In recent years, there has been an increasing demand for molecules with unique structures and properties for various applications, such as pharmaceuticals, agrochemicals, and materials science.
One such molecule that has gained attention in recent times is (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine, a compound with a complex structure and interesting properties.

In this article, we will review the different synthetic routes that have been reported in the literature for the synthesis of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine.
We will discuss the advantages and disadvantages of each method, their reaction conditions, and the yields obtained.

Preparation of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine via Pauling's Condensation:

One of the earliest reported synthetic routes for the preparation of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine was via Pauling's Condensation.
This method involves the reaction of an amine with an aldehyde in the presence of a Lewis acid catalyst, such as BF3*OEt2 or AlCl3.
The reaction is conducted in an inert solvent, such as THF or DMF, at low temperatures (-78°C to -10°C) to prevent undesired side reactions.

Advantages:

• The use of a Lewis acid catalyst enables the reaction to proceed smoothly and efficiently.
  
• The reaction can be carried out at low temperatures, which helps to minimize unwanted side reactions.
  

Disadvantages:

• The reaction requires the use of expensive and hazardous reagents, such as BF3*OEt2 and AlCl3.
  
• The isolated yield of the product is moderate (63% yield).
  

Preparation of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine via Seydenfeld Condensation:

Another method for the synthesis of (2S,3R)-2-[(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine is the Seydenfeld Condensation.
In this method, an amine is reacted with an alcohol in the presence of a reactive alkene, such as but-2-ene or isoprene, and a Lewis acid catalyst, such as BF3*OEt2 or AlCl3.
The reaction is carried out in an inert solvent, such as THF or DMF, at low temperatures (-78°C to -10°C) to prevent undesired side reactions.

Advantages:

• The use of a Lewis acid catalyst enables the reaction to proceed smoothly and efficiently.