Convenient and Scalable Process for the Preparation of Bupropion Hydrochloride via Efficient Bromination of m-Chloropropiophenone with N-Bromosuccinimide

被引：2

作者：

Reddy, Y. Thirupathi ^{[1
]}

Reddy, P. Narsimha ^{[1
]}

Reddy, M. Nikhil ^{[1
]}

Rajitha, B. ^{[1
]}

Crooks, Peter A. ^{[1
]}

机构：

[1] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA

来源：

SYNTHETIC COMMUNICATIONS | 2010年 / 40卷 / 11期

关键词：

-Bromination; bupropion hydrochloride; N-bromosuccinimide; solvent-free; WELLBUTRIN(R); MECHANISM;

D O I：

10.1080/00397910903097351

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A convenient, scalable, and commercially viable process for the production of the antidepressant drug bupropion hydrochloride (1) is reported. The process relies upon an improved, large-scale synthesis of the key intermediate, m-chloro--bromopropiophenone (4). During process development, bromine was replaced with N-bromosuccinimide (NBS) in the presence of para-toluene sulfonic acid (p-TSA), for the bromination of m-chloropropiophenone (3), in either a very low volume of acetonitrile or under solvent-free conditions, to furnish 4. Intermediate 4 was further reacted with t-butylamine in N-methyl-2-pyrrolidinone (NMP) to afford bupropion free base (5), followed by treatment with a saturated solution of hydrochloric acid in isopropyl alcohol (IPA-HCl) to afford bupropion hydrochloride (1). This improved process provides pure bupropion hydrochloride (1) in good yields and at considerably lower cost than existing processes, and it does not involve the use of hazardous reagents.

引用

页码：1566 / 1573

页数：8