The Production Process of 6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-ol

The production process of 6-(trifluoromethyl)-2,3-dihydro-1H-indol-5-ol, also known as 6-TRIF, is a complex and multi-stage process that involves various chemical reactions and purification steps.
The following is an overview of the production process of 6-TRIF in the chemical industry.

1. Synthesis of N-Fmoc-L-phenylalanine-p-nitrophenyl ester
   The first step in the production of 6-TRIF is the synthesis of N-Fmoc-L-phenylalanine-p-nitrophenyl ester, which is a precursor to 6-TRIF.
   This reaction involves the reaction of L-phenylalanine with p-nitrophenyl chloride in the presence of a catalyst, such as PyBOP (para-toluenesulfonic acid), and a solvent, such as DMF (N,N-dimethylformamide).
   
2. Pd/C-catalyzed hydrogenation
   After the synthesis of N-Fmoc-L-phenylalanine-p-nitrophenyl ester, the next step is to reduce the ester to an amine.
   This reaction is catalyzed by Pd/C and is typically carried out in the presence of a solvent, such as EtOH (ethanol) or THF (tetrahydrofuran), and a reducing agent, such as H2 (hydrogen) or NaBH4 (sodium borohydride).
   
3. Deprotection and purification
   The amine obtained from the hydrogenation step is still protected with a Fmoc group, which needs to be removed.
   This step is called deprotection and can be carried out using different methods, such as acid hydrolysis or base cleavage.
   After deprotection, the product is purified by chromatography, typically using a column packed with silica gel.
   
4. Boc-ligation
   The next step is to protect the amine nitrogen with a BOC group.
   This step involves the reaction of the amine with Boc-anhydride, which is typically carried out in the presence of a solvent, such as DMF or DME (dimethoxyethane), and a catalyst, such as DMAP (4-dimethylaminopyridine).
   
5. Halogenation
   The BOC-protected amine is then halogenated to introduce the trifluoromethyl group.
   This reaction is typically carried out using a halogenating reagent, such as PCl3 (phosphorus trichloride), in the presence of a solvent, such as CH2Cl2 (chloroform) or DCM (dichloromethane), and a catalyst, such as Pd/C.
   
6. Hydrolysis
   After the halogenation step, the trifluoromethyl group needs to be protected with a phosphate group.
   This step is called hydrolysis and is typically carried out using a strong acid, such as HCl (hydrochloric acid), in the presence of a solvent, such as water, and a base, such as NaOH (sodium hydroxide), to neutralize the acid.
   
7. Purification
   The product obtained from the hydrolysis step is still acidic and needs to be purified.
   This can be done using different methods, such as chromatography or crystallization.
   
8. Deprotection
   The final step is to remove the BOC and phosphate protecting groups, which can be done using different methods, such as acid hydrolysis or base cleavage.
   

Overall, the production process of 6-TRIF involves several chemical reactions and purification steps.
The process can be carried out using different solvents and reagents, and the choice of reagents and conditions can vary depending on the specific requirements of the manufacturing process.
It is important to note that the production of 6-TRIF requires specialized equipment and facilities and