Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate. / Christensen, Kim Müller; Pedersen, Michael Jønch; Dam-Johansen, Kim; Holm, Thomas Lønberg; Skovby, Tommy; Kiil, Søren.

In: Chemical Engineering Science, Vol. 71, 2012, p. 111-117.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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Christensen, Kim Müller; Pedersen, Michael Jønch; Dam-Johansen, Kim; Holm, Thomas Lønberg; Skovby, Tommy; Kiil, Søren / Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate.

In: Chemical Engineering Science, Vol. 71, 2012, p. 111-117.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

Bibtex

@article{51e2bf8597a54e08a6df30ac50909751,
title = "Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate",
publisher = "Pergamon",
author = "Christensen, {Kim Müller} and Pedersen, {Michael Jønch} and Kim Dam-Johansen and Holm, {Thomas Lønberg} and Tommy Skovby and Søren Kiil",
year = "2012",
doi = "10.1016/j.ces.2011.12.002",
volume = "71",
pages = "111--117",
journal = "Chemical Engineering Science",
issn = "0009-2509",

}

RIS

TY - JOUR

T1 - Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate

A1 - Christensen,Kim Müller

A1 - Pedersen,Michael Jønch

A1 - Dam-Johansen,Kim

A1 - Holm,Thomas Lønberg

A1 - Skovby,Tommy

A1 - Kiil,Søren

AU - Christensen,Kim Müller

AU - Pedersen,Michael Jønch

AU - Dam-Johansen,Kim

AU - Holm,Thomas Lønberg

AU - Skovby,Tommy

AU - Kiil,Søren

PB - Pergamon

PY - 2012

Y1 - 2012

N2 - A novel filter reactor system for continuous production of selected pharmaceutical intermediates is presented and experimentally verified. The filter reactor system consists of a mixed flow reactor equipped with a bottom filter, to retain solid reactant particles, followed by a conventional plug flow reactor, where residual reactant is converted by titration. A chemical case study, production of the pharmaceutical intermediate allylcarbinol by a reaction between allylmagnesium chloride and 2-chloro-thioxanthone, in the presence of a side reaction is considered. The synthesis is conducted in tetrahydrofuran solvent. The use of the filter reactor design was explored by examining the transferability of a synthesis step in a present full-scale semi-batch pharmaceutical production into continuous processing. The main advantages of the new continuous minireactor system, compared to the conventional semi-batch operation, are reduced impurity formation and the use of much lower reactor volumes (factor of 1000 based on the laboratory reactor) and less solvent consumption (from 5.8 to 2.3L/kg reactant). Added challenges include handling of continuous solid powder feeding, stable pumping of reactive slurries, and a possibility of continuous control.

AB - A novel filter reactor system for continuous production of selected pharmaceutical intermediates is presented and experimentally verified. The filter reactor system consists of a mixed flow reactor equipped with a bottom filter, to retain solid reactant particles, followed by a conventional plug flow reactor, where residual reactant is converted by titration. A chemical case study, production of the pharmaceutical intermediate allylcarbinol by a reaction between allylmagnesium chloride and 2-chloro-thioxanthone, in the presence of a side reaction is considered. The synthesis is conducted in tetrahydrofuran solvent. The use of the filter reactor design was explored by examining the transferability of a synthesis step in a present full-scale semi-batch pharmaceutical production into continuous processing. The main advantages of the new continuous minireactor system, compared to the conventional semi-batch operation, are reduced impurity formation and the use of much lower reactor volumes (factor of 1000 based on the laboratory reactor) and less solvent consumption (from 5.8 to 2.3L/kg reactant). Added challenges include handling of continuous solid powder feeding, stable pumping of reactive slurries, and a possibility of continuous control.

KW - Continuous design

KW - Chemical reactors

KW - Batch

KW - Pharmaceuticals

KW - Grignard

KW - Optimization

U2 - 10.1016/j.ces.2011.12.002

DO - 10.1016/j.ces.2011.12.002

JO - Chemical Engineering Science

JF - Chemical Engineering Science

SN - 0009-2509

VL - 71

SP - 111

EP - 117

ER -