Full-Scale Continuous Mini-Reactor Setup for Heterogeneous Grignard Alkylation of a Pharmaceutical Intermediate

Michael Jønch Pedersen; Thomas Holm; Jesper P. Rahbek; Tommy Skovby; Michael James Mealy; Kim Dam-Johansen; Søren Kiil

doi:10.1021/op400069e

Full-Scale Continuous Mini-Reactor Setup for Heterogeneous Grignard Alkylation of a Pharmaceutical Intermediate

Michael Jønch Pedersen, Thomas Holm, Jesper P. Rahbek, Tommy Skovby, Michael James Mealy, Kim Dam-Johansen, Søren Kiil

H. Lundbeck A/S

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

A reactor setup consisting of two reactors in series has been implemented for a full-scale, heterogeneous Grignard alkylation. Solutions pass from a small filter reactor into a static mixer reactor with multiple side entries, thus combining continuous stirred tank reactor (CSTR) and plug flow reactor (PFR) technologies. Through the use of the reactor train in combination with in-line NIR analysis, on scale a 35% reduction in solvent volume was realized, and the formation of a key impurity was suppressed. The mini-reactor solution achieved many of the economic advantages attributed to microreactor technology, while avoiding the difficulties associated with handling of solids in microreactors.

Original language	English
Journal	Organic Process Research and Development
Volume	17
Issue number	9
Pages (from-to)	1142-1148
ISSN	1083-6160
DOIs	https://doi.org/10.1021/op400069e
Publication status	Published - 2013

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title = "Full-Scale Continuous Mini-Reactor Setup for Heterogeneous Grignard Alkylation of a Pharmaceutical Intermediate",

abstract = "A reactor setup consisting of two reactors in series has been implemented for a full-scale, heterogeneous Grignard alkylation. Solutions pass from a small filter reactor into a static mixer reactor with multiple side entries, thus combining continuous stirred tank reactor (CSTR) and plug flow reactor (PFR) technologies. Through the use of the reactor train in combination with in-line NIR analysis, on scale a 35% reduction in solvent volume was realized, and the formation of a key impurity was suppressed. The mini-reactor solution achieved many of the economic advantages attributed to microreactor technology, while avoiding the difficulties associated with handling of solids in microreactors.",

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AU - Pedersen, Michael Jønch

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AU - Skovby, Tommy

AU - Mealy, Michael James

AU - Dam-Johansen, Kim

AU - Kiil, Søren

PY - 2013

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AB - A reactor setup consisting of two reactors in series has been implemented for a full-scale, heterogeneous Grignard alkylation. Solutions pass from a small filter reactor into a static mixer reactor with multiple side entries, thus combining continuous stirred tank reactor (CSTR) and plug flow reactor (PFR) technologies. Through the use of the reactor train in combination with in-line NIR analysis, on scale a 35% reduction in solvent volume was realized, and the formation of a key impurity was suppressed. The mini-reactor solution achieved many of the economic advantages attributed to microreactor technology, while avoiding the difficulties associated with handling of solids in microreactors.

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JF - Organic Process Research and Development

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ER -

Full-Scale Continuous Mini-Reactor Setup for Heterogeneous Grignard Alkylation of a Pharmaceutical Intermediate

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