The Synthetic Routes of (2S,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine

In the world of chemistry, the synthesis of new molecules is a crucial aspect of the field.
The development of new drugs, materials, and other chemical compounds relies on the ability to synthesize novel molecules with specific properties and characteristics.
In this article, we will discuss the synthetic routes of (2S,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine, a molecule with potential applications in the field of chemistry and pharmaceuticals.

The synthesis of (2S,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine involves a multi-step process, with several possible synthetic routes.
One possible synthetic route involves the following steps:

Step 1: Preparation of 3,5-bis(trifluoromethyl)phenyl alcohol

The first step in the synthesis of (2S,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine is the preparation of 3,5-bis(trifluoromethyl)phenyl alcohol.
This can be achieved through the reaction of 3,5-difluoro-methylbenzaldehyde with methyllithium in the presence of a solvent such as THF.

Step 2: Halogenation of 3,5-bis(trifluoromethyl)phenyl alcohol

In the second step, the 3,5-bis(trifluoromethyl)phenyl alcohol is treated with a halogenating agent such as chlorine gas or a chloride salt, in the presence of a solvent such as ether or CHCl3.
This step is necessary to introduce the trifluoromethyl group into the molecule.

Step 3: Nitrostylyation of 3,5-bis(trifluoromethyl)phenyl alcohol

The next step is the nitrostylyation of 3,5-bis(trifluoromethyl)phenyl alcohol, which involves the addition of nitric oxide to the alcohol in the presence of a solvent such as acetonitrile or DMF.
This step is necessary to introduce the nitro group into the molecule.

Step 4: Deprotection of 3,5-bis(trifluoromethyl)-1H-pyrrole-2-one

In the fourth step, the 3,5-bis(trifluoromethyl)-1H-pyrrole-2-one, which is obtained from the nitrostylyation step, is treated with a reducing agent such as lithium aluminum hydride in the presence of a solvent such as ether.
This step is necessary to remove the protecting group from the nitro group and to prepare the molecule for further synthesis.

Step 5: Preparation of 1H-pyrrole-2-one

In the fifth step, a 1H-pyrrole-2-one is prepared through a series of reactions, which involves the reaction of 3,5-bis(trifluoromethyl)-1H-pyrrole-2-one with sodium in the presence of a solvent such as THF.
The pyrrole-2-one is then treated with chloroformic acid and then with sodium hydroxide to obtain the final product.

Step 6: Halogenation of 1H-pyrrole-2-one

In the sixth step, the 1H-pyrrole-2-one is treated with a halogenating agent such as chlorine gas or a chloride salt, in the presence of a solvent such as ether or CHCl3.
This step is necessary to introduce the trifluoromethyl group into the molecule.

Step 7: Nitrostylyation of 1