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Development and Scale-Up of Three Consecutive Continuous Reactions for Production of 6-Hydroxybuspirone

By LaPorte, Thomas L.; Hamedi, Mourad; DePue, Jeffrey S.; Shen, Lifen; Watson, Daniel; Hsieh, Daniel

Published on CMKC

Abstract

This paper describes the development of a continuous, high yielding, and scalable enolization, oxidation, and quench process for the hydroxylation of the azapirone psychtropic agent buspirone to afford 6-hydroxybuspirone (6-hydroxy-8-[4-(4-pyrimidin-2-yl-piperazin-1-yl)-butyl]-8-aza-spiro[4.5]decane-7,9-dione). Two feed streams were reacted continuously using an in-line static mixer followed by oxidation in a continuous flow trickle-bed reactor. The laboratory reactor operation was demonstrated at steady state for over 40 h. The process was scaled up using both volumetric (enolization) and numbering-up (oxidation) scale-up strategies. A pilot-plant reactor was developed and successfully implemented in a three-batch campaign (47 kg input per batch).

Journal

Organic Process Research & Development. Volume 12, 2008, 956-966

DOI

10.1021/op800079u

Type of publication

Peer-reviewed journal

Affiliations

  • Bristol-Myers Squibb

Article Classification

Research article

Classification Areas

  • API

Tags