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

2008; American Chemical Society; Volume: 12; Issue: 5 Linguagem: Inglês

10.1021/op800079u

1520-586X

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

Microfluidic and Capillary Electrophoresis Applications

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).