We are glad to share that this summer, three new papers concerning projects carried at NormandyFlowChem were published:<\/p>\n\n\n\n
The first article presents the process intensification of our continuous flow synthesis of Propofol, an anaesthetic used in intensive care units, is now published in Organic Process Research & Development <\/em>(DOI : https:\/\/doi.org\/10.1021\/acs.oprd.6c00151<\/a>). The second article presents the development and scale-up of a regioselective functionalization of 2-Cyano-3-fluoropyridine, an interesting intermediate towards APIs, is now published in Organic Process Research & Development<\/em> (DOI : https:\/\/doi.org\/10.1021\/acs.oprd.6c00156<\/a>). We are also glad that these two articles were published back-to-back in the last issue of OPRD :)<\/p>\n\n\n\n The third paper describes the controlled use of the halogen dance phenomenon on bromo(thi)azoles thanks to flow chemistry and its exploitation in regioselective functionnalization. It is now published in the Journal of Organic Chemistry<\/em> (DOI : https:\/\/doi.org\/10.1021\/acs.joc.6c00972<\/a>).<\/p>\n\n\n\n This project was conducted by Baran Ozveren<\/a>, Antoine Coeuillas<\/a>, Philippe Jubault<\/a>, Laetitia Chausset-Boissarie<\/a> Thomas Poisson<\/a> and Julien Legros<\/a> within NormandyFlowChem<\/a> plateforme ofInstitut CARMeN<\/a>, in collaboration with the company INTEROR<\/a>. <\/p>\n\n\n\n The process conditions developped allow to maximize the halogen dance (caused by bromine-lithium exchange between a LDA-deprotonated intermediate and the starting material), to trap the obtained lithiated intermediate, and thus to prepare more easily diverse (bis)functionnalized with a very good regioselectivity. This strategy could then become a key step in the synthesis of complex heteroaromatic molecules.<\/p>\n\n\n\n
This project was conducted by Antoine Coeuillas<\/a>, Aurore CEUNINCK, PhD<\/a>, Laetitia Chausset-Boissarie<\/a>, Julien Legros<\/a>, Philippe Jubault<\/a> and Thomas Poisson<\/a> within NormandyFlowChem<\/a> plateforme ofInstitut CARMeN<\/a>. The purpose was to re-optimize our previous 2021 synthesis, with the aim to scale the process while keeping in mind the various industrial constraints. We could increase significatively both productivity and space-time yield of the synthesis, while discarding non-desirables reagents and solvents for industry, resulting in a more sustainable process.
This work has been made possible thanks to NFC plateforme complete range of flow chemisty equipments: Vapourtec Ltd<\/a> systems for initial lab development, then Corning Advanced-Flow Reactors<\/a> (G1) and KHIMOD<\/a> systems for transposition to higher kilolab\/pilot scale.
We also would like to thank Fr\u00e9d\u00e9ric Pin, Sylvie Dhulut and Thibaud Br\u00e9gent from ORIL Industrie for GreenScore calculation, and Eric Aubay<\/a> for the Khimod reactor loan.<\/p>\n\n\n\nDevelopment and Scale-Up of a Regioselective Functionalization of 2-Cyano-3-fluoropyridine in a Flow Reactor, OPRD<\/em><\/a><\/h3>\n\n\n\n
This project was conducted by L\u00e9na Brassart<\/a>, Antoine Coeuillas<\/a>, Thomas Poisson<\/a>, Julien Legros<\/a>, Philippe Jubault<\/a> and Laetitia Chausset-Boissarie<\/a> within NormandyFlowChem<\/a> plateforme ofInstitut CARMeN<\/a>in collaboration with Maxime MANNEVEAU<\/a>, Philippe Huez<\/a> and Massimiliano Forcato<\/a> from the pharmaceutical company Zach – Zambon Chemicals<\/a>. The process consists in the controlled generation of a pyridyllithium intermediate by deprotonation with LDA and trapping with the desired electrophile in non-cryogenic conditions.
Flow chemistry allows to apply this strategy with a very good selectivity and a good productivity, and has made possible a seamless scale-up from lab equipment (LowFlow system from Corning Advanced-Flow Reactors<\/a>) to larger scale (G1 system), multiplying producitivity by 17 without any loss in selectivity.<\/p>\n\n\n\nTaming the Halogen Dance of Bromo(Thi)azoles through Flow Microreactors, JOC<\/em><\/a><\/h3>\n\n\n\n