The Synthetic Routes of ETHYL-4-METHYL PYRIMIDINE-5-CARBOXYLATE

Synthetic Route of ETHYL-4-METHYL PYRIMIDINE-5-CARBOXYLATE in Chemical Industry

Ethyl-4-methyl pyrimidine-5-carboxylate is an important organic compound in the chemical industry.
It is commonly used as an intermediate in the production of various pharmaceuticals, agrochemicals, and other chemical products.
The synthetic routes of ethyl-4-methyl pyrimidine-5-carboxylate have evolved over time, and there are several methods available for its synthesis.

The traditional synthetic route involved the use of Williamson ether synthesis, which involved the treatment of 2-chloroacetamide with lithium aluminum hydride (LiAlH4) to form lithium 2-chloroacetamide followed by treatment with diethyl malonate and sodium hydroxide.
This method was found to be dangerous due to the risk of explosion and the need for high concentrations of reagents.

A safer and more efficient method for the synthesis of ethyl-4-methyl pyrimidine-5-carboxylate is the use of an aqueous hydrogen peroxide system.
In this method, 2-chloro-4-methyl pyrimidine-5-amine is treated with sodium hydroxide to form the corresponding amide, which is then treated with hydrogen peroxide in the presence of a catalyst such as iron or copper.
The reaction is followed by acid hydrolysis to form ethyl-4-methyl pyrimidine-5-carboxylate.

Another synthetic route for ethyl-4-methyl pyrimidine-5-carboxylate involves the use of a palladium-catalyzed coupling reaction.
In this method, 2-chloro-4-methylpyrimidine and 2-bromo-4-methylpyrimidine are treated with a palladium catalyst in the presence of a ligand such as tetrakis(phosphine)sulfur to form a carbon-carbon bond.
The resulting compound is then hydrolyzed to form ethyl-4-methyl pyrimidine-5-carboxylate.

In conclusion, the synthetic routes of ethyl-4-methyl pyrimidine-5-carboxylate have evolved over time, and there are several methods available for its synthesis.
The aqueous hydrogen peroxide system is considered to be safer and more efficient than the traditional Williamson ether synthesis.
The palladium-catalyzed coupling reaction is also an effective method for the synthesis of ethyl-4-methyl pyrimidine-5-carboxylate, and it offers the advantage of generating a single stereoisomer.
The choice of synthetic route depends on the specific requirements of the application, such as cost, yield, and the presence of unwanted side products.
Overall, the synthetic routes of ethyl-4-methyl pyrimidine-5-carboxylate play a critical role in the production of various pharmaceuticals, agrochemicals, and other chemical products.