The Synthetic Routes of Nizatidine

Nizatidine is a histamine H2-receptor antagonist that is commonly used to treat acid-related stomach problems, such as heartburn and indigestion.
It is available under several brand names, including Tagamet and Cimetidine.
The chemical structure of nizatidine is shown below:

Nizatidine can be synthesized through several different routes, each of which involves several chemical reactions.
The most commonly used synthetic route for nizatidine is the aminoglycoside synthesis route, which involves several steps and starting materials.

Step 1: Preparation of Zwitterion
The synthesis of nizatidine begins with the preparation of a zwitterion, which is a chemical species that contains both acidic and basic functional groups.
To prepare the zwitterion, the amino acid L-alanine and the amino acid L-asparagine are reacted in a dehydration reaction using an acid catalyst, such as hydrochloric acid.
The reaction between the two amino acids results in the formation of a beta-hydroxyasparagine zwitterion, as shown below:

Step 2: Formation of N-Methylhydroxylamine
The next step in the synthesis of nizatidine involves the formation of N-methylhydroxylamine, which is a compound that contains a primary amine group and a hydroxyl group attached to the same carbon atom.
To prepare N-methylhydroxylamine, the beta-hydroxyasparagine zwitterion is treated with methyl iodide in the presence of a strong base, such as sodium hydroxide.
The reaction between the zwitterion and methyl iodide results in the formation of N-methylhydroxylamine, as shown below:

Step 3: Formation of N-Methyl-beta-alanine
The next step in the synthesis of nizatidine involves the formation of N-methyl-beta-alanine, which is a compound that contains both a primary amine group and a carboxyl group attached to the same carbon atom.
To prepare N-methyl-beta-alanine, N-methylhydroxylamine is treated with carbon dioxide in the presence of an acid catalyst, such as sulfuric acid.
The reaction between N-methylhydroxylamine and carbon dioxide results in the formation of N-methyl-beta-alanine, as shown below:

Step 4: Formation of N-Methyl-beta-alanine D-Amino-acid
The final step in the synthesis of nizatidine involves the formation of the D-amino acid, which is a stereoisomer of the amino acid L-alanine.
To prepare the D-amino acid, N-methyl-beta-al