The Synthetic Routes of ETHYL 2-CHLORO-4-(TRIFLUOROMETHYL)PYRIMIDINE-5-CARBOXYLATE

Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate is an important intermediate in the synthesis of various pharmaceuticals, agrochemicals, and other chemical products.
The synthesis of this compound can be achieved through several methods, including synthetic routes that utilize both traditional and modern techniques.
In this article, we will discuss some of the most common synthetic routes for the production of ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate.

One of the most widely used synthetic routes involves the reaction of ethyl 2-chloroacetate with 2,4-difluoro-5-nitro-pyrimidine in the presence of a condensing agent such as dicyclohexylcarbodiimide (DCC).
The reaction leads to the formation of a urea intermediate, which can be hydrolyzed using a strong acid to yield the desired carboxylate.
The reaction can be summarized as follows:

Ethyl 2-chloroacetate + 2,4-difluoro-5-nitro-pyrimidine + DCC → Urea intermediate → Hydrolysis → Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

Another synthetic route involves the reaction of ethyl 2-chloroacetate with 2,4-difluoro-5-methyl-oxazolidin-2-one in the presence of a catalyst such as tin(II) chloride.
The reaction leads to the formation of an aldol product, which can be dehydrated to yield the desired carboxylate.
The reaction can be summarized as follows:

Ethyl 2-chloroacetate + 2,4-difluoro-5-methyl-oxazolidin-2-one + SnCl2 → Aldol product → Dehydration → Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

A third synthetic route involves the reaction of ethyl 2-chloroacetate with 2,4-difluoro-5-nitro-pyrimidine in the presence of a base such as sodium hydroxide.
The reaction leads to the formation of a nitrile intermediate, which can be reduced to yield the desired carboxylate.
The reaction can be summarized as follows:

Ethyl 2-chloroacetate + 2,4-difluoro-5-nitro-pyrimidine + NaOH → Nitrile intermediate → Reduction → Ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate

In addition to the above-mentioned synthetic routes, a variety of other methods have also been reported in the literature for the synthesis of ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate.
These methods include the use of microwave irradiation, the application of ultrasound, and the use of alternative reagents and catalysts.

In conclusion, the synthesis of ethyl 2-chloro-4-(trifluoromethyl)pyrimidine-5-carboxylate can be achieved through a variety of synthetic routes, each offering its own advantages and disadvantages.
The choice of route depends on factors such as the availability of reagents and catalysts, the cost and safety of the reaction, and the desired yield and purity of the product.
Regardless of the route chosen, the synthesis of this important intermediate represents a critical step in the production of