The Synthetic Routes of tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate

tert-Butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate is an important intermediate in the synthesis of various pharmaceuticals and agrochemicals.
This article will discuss some of the synthetic routes that are commonly used to synthesize this compound in the chemical industry.

1. Amide synthesis route

The amide synthesis route is one of the most commonly used methods to synthesize tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate.
In this route, the amide intermediate is prepared by the reaction between 2-pyridinecarboxylic acid (1) and 2-chloro-1-propanamine (2) in the presence of a strong acid catalyst, such as sulfuric acid or phosphoric acid.
The reaction is typically carried out in an organic solvent, such as dichloromethane or chloroform, at room temperature.
The resulting amide is then hydrolyzed using a water-immiscible organic solvent, such as ethyl acetate or methyl t-butyl ether, to form the desired carbamate.

1. Hydrolysis of N-Boc-5-bromopyridine-2-carboxamide

Another synthetic route to tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate involves the hydrolysis of N-Boc-5-bromopyridine-2-carboxamide (3), which is synthesized by the reaction between 2-pyridinecarboxylic acid (1) and 2-bromo-1-propanamine (4) in the presence of a condensation agent, such as dicyclohexylcarbodiimide (DCC) or hydroxybenzotriazole (HOBT).
The resulting N-Boc-5-bromopyridine-2-carboxamide is then hydrolyzed using a strong acid, such as hydrochloric acid or sulfuric acid, in the presence of an organic solvent, such as ether or THF.
The resulting carbamate can then be purified by chromatography to obtain the desired product.

1. Other synthetic routes

There are several other synthetic routes to tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate, including the Grignard reaction, the amide formation by using haloacetamides, and the oxidation of 2-chloro-5-bromopyridine with nitric acid.

In conclusion, tert-butyl 5-bromo-3-hydroxypyridin-2-ylcarbamate is an important intermediate in the synthesis of various pharmaceuticals and agrochemicals, and there are several synthetic routes that can be used to synthesize it, including the amide synthesis route, the hydrolysis of N-Boc-5-bromopyridine-2-carboxamide, and other methods.
The choice of route will depend on the specific requirements of the synthesis, including the availability of reagents and the desired yield.