The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. AbstractFluorine is an essential element for life in the developed world that impacts hugely on the general public because many pharmaceuticals, agrochemicals, anaesthetics, materials and air conditioning materials owe their important properties to the presence of fluorine atoms within their structures.All fluorine atoms used in organic chemistry are ultimately sourced from a mined raw material, fluorspar (CaF 2 ), but, given current usage and global reserve estimates, there is only sufficient fluorspar available for a further 100 years. New large scale raw material sources of fluorine are available but must be sufficiently developed for the benefits of fluorinated systems to continue in the long term.1.

In Africa around 625 000 mortalities per annum (20% of HIV/AIDS related deaths) are due to the affects of the Cryptococcal meningitis (CM) fungal infection. Recently, the World Health Organisation (WHO) and the Infectious Disease Society of America (IDSA) recommended that the first line treatment for CM is a combination of amphotericin B and flucytosine, both now WHO Essential Medicines. However, flucytosine is not even registered for use in any African nation due, in part, to its relatively high cost of manufacture and lack of generic manufacturers. Currently, flucytosine is manufactured by an expensive four-step manufacturing process.Here we report a one-step continuous flow process involving the reaction of inexpensive cytosine with fluorine gas using stainless steel tubular laboratory and pilot-scale silicon carbide reactor devices which is readily scaleable to a manufacturing process with a low initial capital expenditure.

Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details.

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Pharmaceutically important chiral fluorolactam derivatives bearing a fluorine atom at a stereogenic centre were synthesized by a route involving copper catalyzed selective direct fluorination using fluorine gas for the construction of the key C-F bond and a biochemical amidase process for the crucial asymmetric cyclisation stage. A comparison of process green metrics with reported palladium catalyzed enantioselective fluorination methodology shows the fluorination-amidase route to be very efficient and more suitable for scale-up.Scheme 1 Examples of reagent combinations used for the synthesis of enantiopure systems with fluorine located at a stereogenic centre. † Electronic supplementary information (ESI) available: For experimental details (SI-1), metrics calculations (SI-2), HPLC analysis (SI-3), X-ray crystallography (SI-4) and NMR spectra

Reaction of low cost, readily available 4 th generation refrigerant gas 2,3,3,3-tetrafluoropropene (HFO-1234yf) with lithium diisopropylamide (LDA) leads to formation of lithium 3,3,3-trifluoropropynide, addition of which to a range of aldehydes formed CF 3-alkynyl alcohol derivatives on multigram scale, which were oxidised using Dess-Martin periodinane (DMP) to give substituted CF 3-ynones with minimal purification required. Michael-type additions of alcohol and amine nucleo-[a] B.

This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C−H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.

(2014) 'Targeted uorination of a nonsteroidal anti-in ammatory drug to prolong metabolic half-life.', ChemMedChem., 9 (4). pp. 733-736. Further information on publisher's website: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details.