The Synthetic Routes of 5-methyl-6-(trifluoromethyl)-2,3-dihydro-1H-indole

5-methyl-6-(trifluoromethyl)-2,3-dihydro-1H-indole is an important intermediate in the synthesis of various pharmaceuticals, agrochemicals, and other industrial chemicals.
The demand for this compound has been increasing rapidly in recent years, making its synthesis a subject of considerable interest in the chemical industry.
There are several synthetic routes available for the preparation of 5-methyl-6-(trifluoromethyl)-2,3-dihydro-1H-indole, each with its own advantages and disadvantages.
In this article, we will discuss some of the most commonly used synthetic routes for the preparation of this compound.

1. Classical Synthesis Route

The classical synthetic route for the preparation of 5-methyl-6-(trifluoromethyl)-2,3-dihydro-1H-indole involves several steps, including the reaction of 5-methyl-2,3-dihydro-1H-indole with 2,3,4,5,6-pentafluoronitrobenzene, followed by reduction of the nitro group using hydrogenation or a reduction agent such as lithium aluminum hydride (LiAlH4).

This route involves the use of hazardous reagents such as nitrobenzene and LiAlH4, and requires careful handling and disposal.
It also involves several steps, which can increase the complexity and cost of the synthesis.

2. Modern Synthesis Route

A more modern synthetic route involves the use of palladium-catalyzed cross-coupling reactions, such as the Suzuki-Miyaura or the Stille coupling reactions.
This route involves the use of less hazardous reagents and can be performed in a single step, reducing the number of steps required for the synthesis.

The Suzuki-Miyaura reaction involves the use of a phosphine ligand, such as Pd(PPh3)4, and a boronic acid derivative of 5-methyl-2,3-dihydro-1H-indole.
The reaction proceeds under mild conditions and can be performed in anhydrous ethyl acetate or other polar protic solvents.
The product can be easily isol