The Synthetic Routes of Isocorydine hydrochloride

Isocorydine hydrochloride is an important pharmaceutical intermediate used in the synthesis of various anti-inflammatory and anti-tumor drugs.
The chemical structure of isocorydine hydrochloride is shown below:

Isocorydine hydrochloride can be synthesized through several synthetic routes, each with its own advantages and disadvantages.
In this article, we will discuss three commonly used synthetic routes for the preparation of isocorydine hydrochloride.

Route 1: via N-Alkylation of 2-Phenylglycine Methyl Ether

This route involves the N-alkylation of 2-phenylglycine methyl ether with a desired alkylating agent, such as methyl iodide or ethyl iodide, followed by hydrolysis of the resulting N-alkyl derivative with a strong acid, such as hydrochloric acid.
The reaction scheme is shown below:

The reaction is typically carried out in the presence of a solvent, such as acetonitrile or dichloromethane, and a base, such as triethylamine or N,N-diisopropylethylamine.
The choice of solvent and base depends on the specific reagents and conditions used.
The product can be isolated by precipitation with a polar solvent, such as ether, or by filtration.

Route 2: via N-Alkylation of 2-Phenylglycine with Alkyl Grignard Reagent

This route involves the formation of a Grignard reagent from 2-phenylglycine and an alkyl halide, such as methyl iodide or ethyl iodide, followed by condensation with a phenol derivative, such as p-toluenesulfonic acid or 4-chloro phenol.
The reaction scheme is shown below:

The reaction is typically carried out in the presence of a Lewis acid catalyst, such as zinc chloride or aluminum chloride, and a solvent, such as ether or hexane.
The product can be isolated by precipitation with a polar solvent, such as ether, or by filtration.

Route 3: via N-Alkylation of 2-Phenylglycine with Hydrazine Halide

This route involves the formation of a hydrazone intermediate from 2-phenylglycine and an hydrazine halide, such as hydrazine monohydrochloride or methyl hydrazine hydrochloride, followed by reduction with a reducing agent, such as lithium aluminum hydride or diisobutylaluminum hydride.
The reaction scheme is shown below:

The reaction is typically carried out in the presence of a solvent, such as acetonitrile or dichloromethane, and a base, such as triethylamine or N,N-diisopropylethylamine.
The product can be isolated by precipitation with a polar solvent, such as ether, or by filtration.

Overall, the