The Synthetic Routes of Esomeprazole magnesium

Esomeprazole magnesium is a popular medication used to treat conditions such as acid reflux and gastroesophageal reflux disease (GERD).
It belongs to a class of drugs called proton pump inhibitors (PPIs), which work by reducing the amount of acid produced by the stomach.
In the chemical industry, the synthesis of Esomeprazole magnesium is a complex process that involves several steps.
In this article, we will discuss the synthetic routes of Esomeprazole magnesium, including the starting materials required, the various reaction mechanisms involved, and the final product.

I.
Starting Materials

The synthesis of Esomeprazole magnesium requires several starting materials.
The most common starting material is 4-[(4,5-dihydroimidazo[1,2-d][1,4]benzoxazepin-3-yl)amino]-2-oxo-1,2-oxazepane, which is also known as lansoprazole.
This compound is available commercially and is used as the starting material for the synthesis of Esomeprazole magnesium.

II.
Synthesis Route 1: 1,4-Diazabicyclo[2.
2.
2]octane (DABCO) route

The first synthetic route for Esomeprazole magnesium involves the use of 1,4-diazabicyclo[2.
2.
2]octane (DABCO) as the starting material.
This route involves several steps, including the protection of the amino group of lansoprazole, the conversion of the lansoprazole intermediate into a quinone methide, and the final step of converting the quinone methide into Esomeprazole magnesium.

The synthesis of Esomeprazole magnesium via the DABCO route involves the following steps:

Step 1: Protection of the Amino Group

In this step, the amino group of lansoprazole is protected with a trimethylsilyl (TMS) group.
This is done to prevent the group from undergoing reactions during the subsequent steps.
The TMS group is attached to the amino nitrogen atom of lansoprazole using a reagent such as diazomethane.

Step 2: Conversion of the Lansoprazole Intermediate into a Quinone Methide

The protected lansoprazole intermediate is then converted into a quinone methide using a reagent such as methyl iodide.
This step involves the reduction of the lansoprazole intermediate to form a methyl ketone, followed by the reaction with methyl iodide to form the quinone methide.

Step 3: Conversion of the Quinone Methide into Esomeprazole Magnesium

The quinone methide is then converted into Esomeprazole magnesium using a reducing agent such as hydrogen gas and a metal catalyst such as palladium on barium sulfate.
This step involves the reduction of the quinone methide to form the final product, Esomeprazole magnesium.

III.
Synthesis Route 2: Nitric Acid Route

The second synthetic route for Esomeprazole magnesium involves the use of nitric acid as the starting material.
This route involves several steps, including the conversion of nitric acid into a diazonium salt, the coupling of the diazonium salt with lansoprazole, and the final step of reducing the diazonium salt into Esomeprazole magnesium.

The synthesis of Esomeprazole magnesium via the nitric acid route involves the following steps:

Step 1: Conversion of Nitric Acid into a Diazonium Salt

In this step, nitric acid is converted into a dia