Continuous-Flow Synthesis of (–)-Oseltamivir Phosphate (Tamiflu)

Herein the anti-influenza drug (–)-oseltamivir phosphate is prepared in continuous flow from ethyl shikimate with 54% overall yield over nine steps and total residence time of 3.5 min from the individual steps. Although the procedure involved intermediate isolation, the dangerous azide chemistry and intermediates involved were elegantly handled in situ. It is the first continuous-flow process for (–)-oseltamivir phosphate involving azide chemistry and (–)-shikimic acid as precursor.

Download Full-text

Continuous flow synthesis of amine oxides by oxidation of tertiary amines

Reaction Chemistry & Engineering ◽

10.1039/c9re00127a ◽

2019 ◽

Vol 4 (7) ◽

pp. 1270-1276

Author(s):

Tobias Baumeister ◽

Stefan Zikeli ◽

Hannes Kitzler ◽

Paul Aigner ◽

Piotr P. Wieczorek ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Continuous Flow ◽

Tertiary Amines ◽

Flow Process ◽

Flow Synthesis ◽

Amine Oxides ◽

Continuous Flow Process

An efficient, safe and scalable continuous flow process for the synthesis of amine oxides with hydrogen peroxide is described.

Download Full-text

A Two-Stage Continuous-Flow Synthesis of Spirooxazine Photochromic Dyes

Australian Journal of Chemistry ◽

10.1071/ch12435 ◽

2013 ◽

Vol 66 (2) ◽

pp. 172 ◽

Cited By ~ 6

Author(s):

Mark York ◽

Adriana Edenharter

Keyword(s):

Continuous Flow ◽

Hydroxylamine Hydrochloride ◽

Preliminary Evaluation ◽

Substituted Anilines ◽

Two Stage ◽

Flow Process ◽

Flow Synthesis ◽

Continuous Flow Process

A continuous-flow process for the synthesis of several known and previously unreported spirooxazine photochromic dyes is reported. The process proceeds via an initial copper catalysed addition of substituted anilines to naphthalene-1,2-dione. This is followed by reaction with 1,3,3-trimethyl-2-methyleneindoline in the presence of hydroxylamine hydrochloride to give the desired spirooxazine products. The photochromic dyes were then cast into lenses to allow a preliminary evaluation of their properties.

Download Full-text

Continuous Flow Synthesis of Propofol

Molecules ◽

10.3390/molecules26237183 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7183

Author(s):

Romain Mougeot ◽

Philippe Jubault ◽

Julien Legros ◽

Thomas Poisson

Keyword(s):

Intensive Care ◽

Intensive Care Medicine ◽

Continuous Flow ◽

Intravenous Anesthesia ◽

Flow Process ◽

Short Acting ◽

Flow Synthesis ◽

Step Procedure ◽

Continuous Flow Process

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.

Download Full-text

Telescoped continuous flow generation of a library of highly substituted 3-thio-1,2,4-triazoles

Reaction Chemistry & Engineering ◽

10.1039/c7re00125h ◽

2017 ◽

Vol 2 (6) ◽

pp. 896-907 ◽

Cited By ~ 6

Author(s):

Mariana C. F. C. B. Damião ◽

Renan Galaverna ◽

Alan P. Kozikowski ◽

James Eubanks ◽

Julio C. Pastre

Keyword(s):

Residence Time ◽

Continuous Flow ◽

Flow Process ◽

Flow Generation ◽

Continuous Flow Process

An integrated continuous flow process for the synthesis of 3-thio-1,2,4-triazoles is reported. A small library of 18 compounds was prepared in just 48 minutes of residence time in moderate to excellent yields.

Download Full-text

Rapid multigram scale end-to-end continuous flow synthesis of sulfonylurea anti-diabetes drugs: Gliclazide, chlorpropamide and tolbutamide

Synthesis ◽

10.1055/a-1664-2282 ◽

2021 ◽

Author(s):

Cloudius Sagandira ◽

Paul Watts

Keyword(s):

Residence Time ◽

Continuous Flow ◽

Flow Synthesis ◽

Sulfonyl Urea ◽

Flow Processes ◽

End To End ◽

Total Residence Time ◽

Sulfonylurea Drugs

Herein we report multigram scale robust, efficient, and safe end-to-end continuous flow processes for the diabetes sulfonylurea drugs gliclazide, chlorpropamide and tolbutamide. The drugs were prepared via the treatment of an amine with a haloformate affording carbamate which was subsequently treated with a sulfonamide to afford sulfonylurea. Gliclazide was afforded in 87 % yield within 2.5 min total residence time with 26 g/h throughput; 0.2 Kg of the drug was produced in 8 h of running the system continuously. Chlorpropamide and tolbutamide were both afforded in 94 % yield within 1 min residence time with 184-188 g/h throughput; 1.4-1.5 Kg of the drugs was produced in 8 h of running the system continuously. N-substituted carbamates were used as safe alternatives to the hazardous isocyanates in constructing the sulfonyl urea moiety.

Download Full-text

Development of a Continuous Photochemical Benzyne-Forming Process

SynOpen ◽

10.1055/s-0040-1706016 ◽

2021 ◽

Vol 05 (01) ◽

pp. 29-35

Author(s):

Marcus Baumann ◽

Cormac Bracken ◽

Andrei S. Batsanov

Keyword(s):

Residence Time ◽

High Power ◽

Continuous Flow ◽

Forming Process ◽

Flow Process ◽

Short Residence Time ◽

High Power Led ◽

Continuous Flow Process ◽

Rapid Generation ◽

By Products

AbstractA continuous-flow process is presented that enables the safe generation and derivatization of benzyne under photochemical conditions. This is facilitated by a new high-power LED lamp emitting light at 365 nm. The resulting flow process effectively controls the release of gaseous by-products based on an adjustable backpressure regulator and delivers a series of heterocyclic products in a short residence time of 3 minutes. The robustness of this methodology is demonstrated for the rapid generation of benzotriazoles, 2H-indazoles and various furan-derived adducts, facilitating the preparation of these important heterocyclic scaffolds via a simple and readily scalable flow protocol.

Download Full-text