Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Continuous flow synthesis of Celecoxib from 2-bromo-3,3,3-trifluoropropene.

ABSTRACT: We describe the total flow synthesis of the widely prescribed anti-inflammatory COX-2 inhibitor Celecoxib from 2-bromo-3,3,3-trifluoropropene, as a convenient and available trifluoromethyl building block, to generate trifluoropropynyl lithium and to trap it immediately with an aldehyde. Oxidation of the obtained alcohol into ketone followed by condensation with 4-sulfamidophenylhydrazine afforded the targeted drug with full regioselectivity. It is noteworthy that the quality of these flow reactions (50% overall yield within 1 h cumulated residence time over 3 steps) directly furnished the target API and intermediates with excellent purity.

Supplementary information

The online version contains supplementary material available at 10.1007/s41981-021-00205-x.

SUBMITTER: Ivanova M

PROVIDER: S-EPMC8491450 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Continuous Flow Synthesis of Propofol.

Project description:Herein, we report a continuous flow process for the synthesis of 2,6-diisopropylphenol-also known as Propofol-a short-acting intravenous anesthesia, widely used in intensive care medicine to provide sedation and hypnosis. The synthesis is based on a two-step procedure: a double Friedel-Crafts alkylation followed by a decarboxylation step, both under continuous flow.

| S-EPMC8659244 | biostudies-literature

Glycol-Thermal Continuous Flow Synthesis of Graphene Gel.

Project description:Hydrothermal treatment of graphene oxide (GO) aqueous dispersion has been extensively applied to create graphene (a.k.a., chemically modified graphene, or reduced GO) hydrogels, which were dried to yield high-density graphene monoliths and powders with promising potential for electrochemical energy storage applications. Here, we demonstrated a glycol-thermal route that allows the preparation of a graphene gel at around 150 °C, which is below the boiling point of ethylene glycol (EG) and thus eliminates the need for a sealed pressurized reaction vessel. As a result, flow synthesis can be achieved by flowing a GO dispersion in EG through a Teflon tube immersed in a preheated oil bath for continuous production of a graphene gel, which, upon drying, shrinks to yield a densified graphene solid.

| S-EPMC8319937 | biostudies-literature

Low-Temperature Continuous Flow Synthesis of Metal Ammonium Phosphates.

Project description:The synthesis of the high performance inorganic materials essential to the quality of modern day life is hindered by traditionalist attitudes and reliance on outdated methods such as batch syntheses. While continuous flow methods have been extensively adopted in pharmaceutical circles, they remain largely unexplored for the preparation of inorganic compounds, despite higher efficiency, safety and versatility. In this publication, we demonstrate a step-change for the synthesis of metal ammonium phosphates through conversion of the extant batch process to a low-temperature continuous regime, exhibiting a tenfold increase in throughput combined with a significant decrease in particle size.

| S-EPMC6131346 | biostudies-literature

Controlled synthesis of poly(3-hexylthiophene) in continuous flow.

Project description:There is an increasing demand for organic semiconducting materials with the emergence of organic electronic devices. In particular, large-area devices such as organic thin-film photovoltaics will require significant quantities of materials for device optimization, lifetime testing and commercialization. Sourcing large quantities of materials required for the optimization of large area devices is costly and often impossible to achieve. Continuous-flow synthesis enables straight-forward scale-up of materials compared to conventional batch reactions. In this study, poly(3-hexylthiophene), P3HT, was synthesized in a bench-top continuous-flow reactor. Precise control of the molecular weight was demonstrated for the first time in flow for conjugated polymers by accurate addition of catalyst to the monomer solution. The P3HT samples synthesized in flow showed comparable performance to commercial P3HT samples in bulk heterojunction solar cell devices.

| S-EPMC3740766 | biostudies-literature

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution.

Project description:We have developed the continuous-flow synthesis of thioureas in a multicomponent reaction starting from isocyanides, amidines, or amines and sulfur. The aqueous polysulfide solution enabled the application of sulfur under homogeneous and mild conditions. The crystallized products were isolated by simple filtration after the removal of the co-solvent, and the sulfur retained in the mother liquid. Presenting a wide range of thioureas synthesized by this procedure confirms the utility of the convenient continuous-flow application of sulfur.

| S-EPMC7827778 | biostudies-literature

Automated synthesis of prexasertib and derivatives enabled by continuous-flow solid-phase synthesis.

Project description:Recent advances in end-to-end continuous-flow synthesis are rapidly expanding the capabilities of automated customized syntheses of small-molecule pharmacophores, resulting in considerable industrial and societal impacts; however, many hurdles persist that limit the number of sequential steps that can be achieved in such systems, including solvent and reagent incompatibility between individual steps, cumulated by-product formation, risk of clogging and mismatch of timescales between steps in a processing chain. To address these limitations, herein we report a strategy that merges solid-phase synthesis and continuous-flow operation, enabling push-button automated multistep syntheses of active pharmaceutical ingredients. We demonstrate our platform with a six-step synthesis of prexasertib in 65% isolated yield after 32 h of continuous execution. As there are no interactions between individual synthetic steps in the sequence, the established chemical recipe file was directly adopted or slightly modified for the synthesis of twenty-three prexasertib derivatives, enabling both automated early and late-stage diversification.

| S-EPMC8054510 | biostudies-literature

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine.

Project description:Numerous synthetic methods for the continuous preparation of fine chemicals and active pharmaceutical ingredients (API's) have been reported in recent years resulting in a dramatic improvement in process efficiencies. Herein we report a highly efficient continuous synthesis of the antimalarial drug hydroxychloroquine (HCQ). Key improvements in the new process include the elimination of protecting groups with an overall yield improvement of 52% over the current commercial process. The continuous process employs a combination of packed bed reactors with continuous stirred tank reactors for the direct conversion of the starting materials to the product. This high-yielding, multigram-scale continuous synthesis provides an opportunity to achieve increase global access to hydroxychloroquine for treatment of malaria.

| S-EPMC5852550 | biostudies-other

Synthesis of 3,3,3-trifluoroethyl isocyanate, carbamate and ureas. Anticancer activity evaluation of N-(3,3,3-trifluoroethyl)-N'-substituted ureas.

Project description:A new method is described for producing 3,3,3-trifluoroethyl isocyanate from perfluoroisobutene (PFIB). Isocyanate was used for synthesis of carbamates and ureas. A series of trifluoroethyl-substituted ureas has been tested in the National Cancer Institute (NCI, Bethesda, USA) by the NCI-60 DTP Human Tumor Cell Line Screening Program at a single high dose (10(-5) M). The moderate anticancer activity was shown against some types of cancer on the individual human cell lines for leukemia, non-small cell lung cancer and renal cancer.

| S-EPMC4511494 | biostudies-literature

Continuous-Flow Synthesis of ZIF-8 Biocomposites with Tunable Particle Size.

Project description:Zeolitic imidazolate framework (ZIF) biocomposites show the capacity to protect and deliver biotherapeutics. To date, the progress in this research area is based on laboratory batch methods. Now, the first continuous flow synthetic method is presented for the encapsulation of a model protein (bovine serum albumin, BSA) and a clinical therapeutic (?1-antitrypsin, AAT) in ZIF-8. The in?situ kinetics of nucleation, growth, and crystallization of BSA@ZIF-8 were studied by small-angle X-ray scattering. By controlling the injection time of ethanol, the particle growth could be quenched by ethanol-induced crystallization from amorphous particles to ZIF-8 crystals. The particle size of the biocomposite was tuned in the 40-100?nm range by varying residence time prior to introduction of ethanol. As a proof-of-concept, this procedure was used for the encapsulation of AAT in ZIF-8. Upon release of the biotherapeutic from the composite, the trypsin inhibitor function of AAT was preserved.

| S-EPMC7318291 | biostudies-literature

Advanced Real-Time Process Analytics for Multistep Synthesis in Continuous Flow*.

Project description:In multistep continuous flow chemistry, studying complex reaction mixtures in real time is a significant challenge, but provides an opportunity to enhance reaction understanding and control. We report the integration of four complementary process analytical technology tools (NMR, UV/Vis, IR and UHPLC) in the multistep synthesis of an active pharmaceutical ingredient, mesalazine. This synthetic route exploits flow processing for nitration, high temperature hydrolysis and hydrogenation reactions, as well as three inline separations. Advanced data analysis models were developed (indirect hard modeling, deep learning and partial least squares regression), to quantify the desired products, intermediates and impurities in real time, at multiple points along the synthetic pathway. The capabilities of the system have been demonstrated by operating both steady state and dynamic experiments and represents a significant step forward in data-driven continuous flow synthesis.

| S-EPMC8048486 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data