Scalable Synthesis of High-Purity (R, R)-Dexmethylphenidate Free Base

Guan Wang,Yuanyuan Sun,Dongsheng Chen,Qing Cao,Jianqi Li,Bonan Li

doi:10.5539/ijc.v8n4p28

Guan Wang, Yuanyuan Sun + Show 4 more

Open Access

https://doi.org/10.5539/ijc.v8n4p28

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Abstract

<p>A practical method for the preparation of high-purity (<em>R, R</em>)-dexmethylphenidate free base was developed. The method involves a substitution reaction of 2-chloropyridine and phenylacetonitrile via hydrolysis followed by hydrogenation, configuration inversion, chiral resolution, methyl esterification, and salification to give high-purity dexmethylphenidate hydrochloride. The hydrochloride salt was then neutralized by powder sodium hydroxide overnight to give dexmethylphenidate free base with over 99% purity. This method can be used for the industrial production of the dexmethylphenidate patch API, which could also be further applied for the preparation of other types of amino acid ester free bases.</p>

Highlights

The hydrochloride salt was neutralized by powder sodium hydroxide overnight to give dexmethylphenidate free base with over 99% purity
This method can be used for the industrial production of the dexmethylphenidate patch API, which could be further applied for the preparation of other types of amino acid ester free bases
The dexmethylphenidate hydrochloride slow-release capsule was developed by Novartis Inc. (Har et al, 2000), and it was approved by the US Food and Drug Administration (FDA) in May 2005 for the treatment of attention deficit hyperactivity disorder (ADHD) (Volkmar et al, 2003), which is the most commonly diagnosed behavioral disorder in children

Summary

Introduction

The dexmethylphenidate hydrochloride slow-release capsule was developed by Novartis Inc. (Har et al, 2000), and it was approved by the US Food and Drug Administration (FDA) in May 2005 for the treatment of attention deficit hyperactivity disorder (ADHD) (Volkmar et al, 2003), which is the most commonly diagnosed behavioral disorder in children. The hydrochloride salt was neutralized by powder sodium hydroxide overnight to give dexmethylphenidate free base with over 99% purity.

Results

Conclusion