Packed bed reactions

An Enzymatic Flow-Based Preparative Route to Vidarabine

Lucia Tamborini¹*, Clelia Previtali¹, Francesca Annunziata¹, Teodora Bavaro², Marco Terreni², Enrica Calleri², Francesca Rinaldi², Andrea Pinto³, Giovanna Speranza⁴, Daniela Ubiali²*, Paola Conti¹

• ¹Department of Pharmaceutical Sciences, University of Milan, via Mangiagalli 25, 20133 Milano, Italy
• ²Department of Drug Sciences, University of Pavia, viale Taramelli 12, 27100 Pavia, Italy
• ³Department of Food, Environmental and Nutritional Sciences, University of Milan, via Celoria 2, 20133 Milano, Italy
• ⁴Department of Chemistry, University of Milan, via Golgi 19, 20133 Milano, Italy

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Enhanced mixing of biphasic liquid-liquid systems for the synthesis of gem-dihalocyclopropanes using packed bed reactors

T von Keutz^1,2, D Cantillo^1,2, CO Kappe^1,2

• ¹ Center for Continuous Flow Synthesis and Processing (CCFLOW) Research Center Pharmaceutical Engineering GmbH (RCPE) Graz, Austria
• ² Institute of Chemistry, NAWI Graz, University of Graz, Graz, Austria

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Copper mediated, heterogeneous, enantioselective intramolecular Buchner reactions of α-diazoketones using continuous flow processing

DC Crowley^†, D Lynch^†, AR Maguire^‡

• ^† School of Chemistry, Analytical and Biological Chemistry Research Facility, University College Cork, Cork T12 K8AF, Ireland
• ^‡ School of Chemistry and School of Pharmacy, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre, University College Cork, Cork T12 K8AF, Ireland

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Continuous flow biocatalysis: production and in-line purification of amines by immobilised transaminase from Halomonas elongata

Matteo Planchestainer^a, Martina Letizia Contente^ab, Jennifer Cassidy^a, Francesco Molinari^b, Lucia Tamborini^*c, Francesca Paradisi^*ad

• ^* Corresponding authors
• ^a UCD School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland
• ^b Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli studi di Milano, Via Mangiagalli 25, Milan, Italy
• ^c Department of Pharmaceutical Sciences (DISFARM), Università degli studi di Milano, Via Mangiagalli 25, Milan, Italy
• ^d School of Chemistry, University of Nottingham, University Park, Nottingham, UK

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Continuous Reductions and Reductive Aminations Using Solid Sodium borohydride

Kerry Gilmore^†, Stella Vukelic^‡, D. Tyler McQuade^†§, Beate Koksch^‡, Peter H. Seeberger^*†‡

• ^† Max Planck Institute of Colloids and Interfaces, Germany
• ^‡ Institute of Chemistry and Biochemistry, Freie Universität Berlin, Germany
• ^§ Department of Chemistry and Biochemistry, Florida State University, United States

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Flow Alkylation of Thiols, Phenols, and Amines Using a Heterogenous Base in a Packed-Bed Reactor

Alastair Baker¹, Michael Graz², Robert Saunders², Gareth J. S. Evans², Ilaria Pitotti1 Thomas Wirth¹

• ¹ School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff CF10 3AT, UK
• ² Neem Biotech, Willowbrook Technical Units, Llandogo Road, St. Mellons, Cardiff CF3 0EF, UK

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An efficient continuous flow process for the synthesis of a non-conventional mixture of fructooligosaccharides

Paolo Zambelli^a, Lucia Tamborini^b, Samuele Cazzamalli^b, Andrea Pinto^b, Stefania Arioli^a, Silvia Balzaretti^a, Francisco J. Plou^c, Lucia Fernandez-Arrojo^c, Francesco Molinari^a, Paola Conti^b, Diego Romano^a

• ^a Department of Food Environmental and Nutritional Science (DeFENS), University of Milan, Via Mangiagalli, 20133 Milan, Italy
• ^b Department of Pharmaceutical Sciences (DISFARM), University of Milan, Via Mangiagalli 25, 20133 Milan, Italy
• ^c Instituto de Catálisis y Petroleoquímica, CSIC, 28049 Madrid, Spain

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Flow synthesis of organic azides and the multistep synthesis of imines and amines using a new monolithic triphenylphosphine reagent

Catherine J. Smith, Christopher D. Smith, Nikzad Nikbin, Steven V. Ley, Ian R. Baxendale

• Innovative Technology Centre, Cambridge, UK

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The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions

Steffen Glöckner, Duc N. Tran, Richard J. Ingham, Sabine Fenner, Zoe E. Wilson, Claudio Battilocchio, Steven V. Ley^*

• Department of Chemistry, University of Cambridge, Cambridge, UK

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Continuous Synthesis of Organozinc Halides Coupled to Negishi Reactions

Nerea Alonso^2,3, L. Zane Miller¹, Juan de M. Muñoz2, Jesus Alcázar^2,*, D. Tyler McQuade^1,*

• ¹Department of Chemistry and Biochemistry, Florida State University, USA
• ²Janssen Research and Development, Janssen-Cilag, Toledo, Spain
• ³Facultad de Química, Universidad de Castilla-La Mancha, Spain

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Integration of enabling methods for the automated flow preparation of piperazine-2-carboxamide

Richard J. Ingham¹, Claudio Battilocchio¹, Joel M. Hawkins², Steven V. Ley¹

• ¹ Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK
• ² Pfizer Worldwide Research and Development, Eastern Point Road, Groton, CT 06340, USA

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Robust and reusable supported palladium catalysts for cross-coupling reactions in flow

William R. Reynolds^ab, Pawel Plucinskib^c, Christopher G. Frost^*ab

•   ^* Corresponding authors
• ^a Centre for Sustainable Chemical Technologies, University of Bath, Claverton Down, Bath, UK
• ^b Department of Chemistry, University of Bath, Claverton Down, Bath, UK
• ^c Department of Chemical Engineering, University of Bath, Claverton Down, Bath, UK

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Flow-Based, Cerium Oxide Enhanced, Low-Level Palladium Sonogashira and Heck Coupling Reactions by Perovskite Catalysts

Claudio Battilocchio¹, Benjamin N. Bhawal¹, Rajeev Chorghade¹, Benjamin J. Deadman¹, Joel M. Hawkins², Steven V. Ley¹

• ¹ Innovative Technology Centre, Department of Chemistry, University of Cambridge, UK
• ² Pfizer Worldwide Research & Development, Groton, USA

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The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

Kimberley A. Roper¹, Malcolm B. Berry², Steven V. Ley¹

• ¹ Innovative Technology Centre, Department of Chemistry, University of Cambridge, Cambridge, U.K.
• ² GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, U.K.

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The rapid generation of isothiocyanates in flow

Marcus Baumann, Ian R. Baxendale

• Department of Chemistry, University of Durham, U.K.

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Continuous Synthesis and Use of N-Heterocyclic Carbene Copper(I) Complexes from Insoluble Cu2O

Suzanne M. Opalka¹, Jin Kyoon Park³, Ashley R. Longstreet², D. Tyler McQuade²

• ¹Department of Chemistry and Biochemistry, Florida State University, USA
• ²Department of Chemistry and Chemical Biology, Cornell University, USA
• ³Department of Chemistry and Chemical Institute for Functional Materials, Pusan National University, Korea

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An expeditious synthesis of imatinib and analogues utilising flow chemistry methods

Mark D Hopkin, Ian Baxendale, Steven.V.Ley

• Dept of Chemistry, University of Cambridge, UK

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A “Catch-React-Release” Method for the Flow Synthesis of 2-Aminopyrimidines and Preparation of the Imatinib Base

Richard J. Ingham, Elena Riva, Nikzad Nikbin, Ian R. Baxendale, Steven V. Ley^*

• Innovative Technology Centre, University of Cambridge, U.K.

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Continuous proline catalysis via leaching of solid proline

Suzanne M. Opalka¹, Ashley R. Longstreet², D. Tyler McQuade²

• ¹Department of Chemistry and Chemical Biology, Cornell University, USA
• ²Department of Chemistry and Biochemistry, Florida State University,USA

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The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

Kimberley A. Roper¹, Heiko Lange¹, Anastasios Polyzos¹, Malcolm B. Berry², Ian R. Baxendale¹, Steven V. Ley¹

• ¹Innovative Technology Centre, University of Cambridge
• ²GlaxoSmithKline, Stevenage, UK

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Suzuki-Miyaura Cross-Coupling of Heteroaryl Halides and Arylboronic Acids in Continuous Flow

Timothy Noël, Andrew J. Musacchio

• Department of Chemistry, MIT, USA

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An Integrated Flow and Batch-Based Approach for the Synthesis of O-Methyl Siphonazole

Marcus Baumann, Ian R. Baxendale, Malte Brasholz, John J. Hayward, Steven V. Ley, Nikzad Nikbin

• Innovative Technology Centre, Cambridge, UK

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Synthesis of (+)-Dumetorine and Congeners by Using Flow Chemistry Technologies

Elena Riva², Anna Rencurosi¹, Stefania Gagliardi¹, Daniele Passarella², Marisa Martinelli^1*

• ¹NiKem Research S.r.l., Milan, Italy
• ²Università degli Studi di Milano,Milan, Italy

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Oxidation Reactions in Segmented and Continuous Flow Chemical Processing Using an N-(tert-Butyl)phenylsulfinimidoyl Chloride Monolith

Heiko Lange, Matthew J. Capener, Alexander X. Jones, Catherine J. Smith, Nikzad Nikbin, Ian R. Baxendale, Steven V. Ley^*

• Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

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A fully automated, multistep flow synthesis of 5-amino-4-cyano-1,2,3-triazoles

Catherine J. Smith, Nikzad Nikbin, Steven V. Ley, Heiko Lange, Ian R. Baxendale

• Innovative Technology Centre, Cambridge, UK

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A breakthrough method for the accurate addition of reagents in multi-step segmented flow processing

Heiko Lange¹, Catherine F. Carter¹, Mark D. Hopkin¹, Adrian Burke², Jon G. Goode², Ian R. Baxendale¹, Steven V. Ley¹

• ¹Innovative Technology Centre, University of Cambridge, UK
• ²Mettler-Toledo AutoChem UK

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Safe and Reliable Synthesis of Diazoketones and Quinoxalines in a Continuous Flow Reactor

Laetitia J. Martin¹, Andreas L. Marzinzik¹, Steven V. Ley², Ian R. Baxendale²

• ¹Novartis Institute for BioMedical Research, Basel, Switzerland
• ²Innovative Technology Centre, Department of Chemistry, University of Cambridge

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A Continuous Flow Process Using a Sequence of Microreactors with In-line IR Analysis for the Preparation of N,N-Diethyl-4-(3-fluorophenylpiperidin-4-ylidenemethyl)benzamide as a Potent and Highly Selective δ-Opioid Receptor Agonist

Zizheng Qian, Ian R. Baxendale, Steven V. Ley

• Innovative Technology Centre, University of Cambridge

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Synthesis of Highly Substituted Nitropyrrolidines, Nitropyrrolizines and Nitropyrroles via Multicomponent-Multistep Sequences within a Flow Reactor

Marcus Baumann, Ian R. Baxendale, Andreas Kirschning, Steven V. Ley^*, Jens Wegner

• Department of Chemistry, University of Cambridge

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A highly efficient flow reactor process for the synthesis of N-Boc-3,4-dehydro-l-proline methyl ester

Lucia Tamborini, Paola Conti, Andrea Pinto, Carlo De Micheli

• Dipartimento di Scienze Farmaceutiche ‘Pietro Pratesi’,
• Università degli Studi di Milano, Italy

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Multistep Synthesis Using Modular Flow Reactors: Bestmann-Ohira Reagent for the Formation of Alkynes and Triazoles

Ian R. Baxendale¹, Steven V. Ley¹, Andrew C. Mansfield², Christopher D. Smith¹

• ¹ITC, Department of Chemistry, University of Cambridge,
• ²Pfizer Global R&D Research Centre, Sandwich, (UK)

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A Bifurcated Pathway to Thiazoles and Imidazoles Using a Modular Flow Microreactor

Ian R. Baxendale, Steven V. Ley, Christopher D. Smith, Lucia Tamborini, Ana-Florina Voica

• Innovative Technology Centre, Cambridge, UK

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The Use of Diethylaminosulfur Trifluoride (DAST) for Fluorination in a Continuous-Flow Microreactor

Baumann, Marcus, Baxendale, Ian R., Ley, Steven V.

• Innovative Technology Centre, Cambridge, UK

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Tagged phosphine reagents to assist reaction work-up by phase-switched scavenging using a modular flow reactor

Christopher D. Smith, Ian Baxendale, Geoffrey Tranmer, Marcus Baumann, Stephen Smith, Russell Lewthwaite, Steven V. Ley

• Department of Chemistry, University of Cambridge, UK

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Fully Automated Flow-Through Synthesis of Secondary Sulfonamides in a Binary Reactor System

Charlotte M. Griffiths-Jones, Mark D. Hopkin, Daniel Jönsson, Steven V. Ley, David J. Tapolczay, Emma Vickerstaffe, Mark Ladlow

• GlaxoSmithKline Cambridge Technology Centre, Cambridge

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A flow reactor process for the synthesis of peptides utilizing immobilized reagents, scavengers and catch and release protocols

Ian R. Baxendale, Steven V. Ley, Christopher D. Smith, Geoffrey K. Tranmer

• Innovative Technology Centre, Cambridge, UK

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