scholarly journals N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1985 ◽  
Author(s):  
György Orsy ◽  
Ferenc Fülöp ◽  
István M. Mándity
Keyword(s):  
Carboxylic Acid ◽  
Continuous Flow ◽  
Scale Up ◽  
Drug Substance ◽  
Aliphatic Amines ◽  
Aromatic And Aliphatic Amines

A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.

scholarly journals A Photocatalytic Regioselective Hydroaminoalkylation of Aryl-Substituted Alkenes with Simple Amines

2021 ◽  
Author(s):  
Natalia Larionova ◽  
Jun Miyatake Ondozabal ◽  
Emily G. Smith ◽  
Xacobe Cambeiro
Keyword(s):  
Continuous Flow ◽  
Scale Up ◽  
Aliphatic Amines ◽  
Flow Conditions ◽  
Unsaturated Esters ◽  
Aniline Derivatives ◽  
Aromatic Group ◽  
Regioselective Addition

A photocatalytic method for the alpha-selective hydroaminoalkylation of cinnamate esters has been developed. The reaction involves the regioselective addition of alpha-aminoalkyl radicals generated from aniline derivatives or aliphatic amines to the alpha-position of unsaturated esters. The scope of aromatic alkenes was extended to styrenes undergoing hydroaminoalkylation with anti-Markovnikov selectivity, which confirms the importance of the aromatic group at the beta-position. Simple scale-up is demonstrated under continuous-flow conditions, highlighting the practicality of the method.<br>

scholarly journals A Photocatalytic Regioselective Hydroaminoalkylation of Aryl-Substituted Alkenes with Simple Amines

2021 ◽  
Author(s):  
Natalia Larionova ◽  
Jun Miyatake Ondozabal ◽  
Emily G. Smith ◽  
Xacobe Cambeiro
Keyword(s):  
Continuous Flow ◽  
Scale Up ◽  
Aliphatic Amines ◽  
Flow Conditions ◽  
Unsaturated Esters ◽  
Aniline Derivatives ◽  
Aromatic Group ◽  
Regioselective Addition

A photocatalytic method for the alpha-selective hydroaminoalkylation of cinnamate esters has been developed. The reaction involves the regioselective addition of alpha-aminoalkyl radicals generated from aniline derivatives or aliphatic amines to the alpha-position of unsaturated esters. The scope of aromatic alkenes was extended to styrenes undergoing hydroaminoalkylation with anti-Markovnikov selectivity, which confirms the importance of the aromatic group at the beta-position. Simple scale-up is demonstrated under continuous-flow conditions, highlighting the practicality of the method.<br>

Design of a continuous flow immobilized-cell reactor for biosynthetical production of L-aspartic acid

1985 ◽  
Vol 50 (10) ◽  
pp. 2122-2133 ◽  
Author(s):  
Jindřich Zahradník ◽  
Marie Fialová ◽  
Jan Škoda ◽  
Helena Škodová
Keyword(s):  
Aspartic Acid ◽  
Continuous Flow ◽  
Immobilized Cells ◽  
Scale Up ◽  
Fixed Bed ◽  
Packed Bed ◽  
Fixed Bed Reactor ◽  
Experimental Program ◽  
Design Parameters ◽  
Immobilized Cell

An experimental study was carried out aimed at establishing a data base for an optimum design of a continuous flow fixed-bed reactor for biotransformation of ammonium fumarate to L-aspartic acid catalyzed by immobilized cells of the strain Escherichia alcalescens dispar group. The experimental program included studies of the effect of reactor geometry, catalytic particle size, and packed bed arrangement on reactor hydrodynamics and on the rate of substrate conversion. An expression for the effective reaction rate was derived including the effect of mass transfer and conditions of the safe conversion-data scale-up were defined. Suggestions for the design of a pilot plant reactor (100 t/year) were formulated and decisive design parameters of such reactor were estimated for several variants of problem formulation.

scholarly journals Diels–Alder reactions of myrcene using intensified continuous-flow reactors

2017 ◽  
Vol 13 ◽  
pp. 120-126 ◽  
Author(s):  
Christian H Hornung ◽  
Miguel Á Álvarez-Diéguez ◽  
Thomas M Kohl ◽  
John Tsanaktsidis
Keyword(s):  
Continuous Flow ◽  
Flow Reactor ◽  
Scale Up ◽  
Reaction Times ◽  
Alder Reaction ◽  
Diels Alder ◽  
Flow Reactors ◽  
Diels Alder Reaction ◽  
Naturally Occurring ◽  
Continuous Flow Reactors

This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This continuous-flow approach provides a facile alternative scale-up route to conventional batch processing, and it helps to intensify the synthesis protocol by applying higher reaction temperatures and shorter reaction times.

scholarly journals Accelerating manufacturing to start large-scale supply of a new adenovirus-vectored vaccine within 100 days

2021 ◽  
Author(s):  
Carina CD Joe ◽  
Rameswara R Segireddy ◽  
Cathy Oliveira ◽  
Adam Berg ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Production Process ◽  
Large Scale ◽  
Scale Up ◽  
Adenovirus Vector ◽  
Drug Substance ◽  
Economic Modelling ◽  
New Production ◽  
Bulk Drug ◽  
Vectored Vaccine ◽  
Manufacturing Network

The Coalition for Epidemic Preparedness Innovations &rsquo &lsquo 100-day moonshot &rsquo aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint. We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity. Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical surge campaign with suitable prior preparation and resources, including adequate fill-and-finish capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.

Iron-Catalyzed One-pot Synthesis of Indole-tethered Tetrasubstituted Pyrroles and Their Transformations to Indolizino[8,7-b]indole Derivatives

Synthesis ◽  
2021 ◽  
Author(s):  
Xue Xiao ◽  
Xiao-Hui Chen ◽  
Xian-Xun Wang ◽  
Wan-Zhen Li ◽  
Hai-Lei Cui
Keyword(s):  
Aliphatic Amines ◽  
Electrophilic Cyclization ◽  
Indole Derivatives ◽  
One Pot ◽  
One Pot Synthesis ◽  
Aromatic And Aliphatic Amines

We have developed an efficient iron-catalyzed one-pot reaction of tryptamines, ynones and nitroolefins affording indole-tethered tetrasubstituted pyrroles in acceptable to good yields. Other aromatic and aliphatic amines can also be utilized in this process delivering corresponding highly functionalized tetrasubstituted pyrroles. Indolizino[8,7-b]indole derivatives could be obtained through TFA, TfOH or Fe(OTf)3-mediated cyclizations via dearomatization of indole. Unexpected dibrominated products, 7,9-dibromo-6,11-dihydro-5H-indolizino[8,7-b]indoles, were formed when PTAP was employed as electrophilic cyclization promoter.

Flow-oriented synthetic design in the continuous preparation of the aryl piperazine drug flibanserin

2019 ◽  
Vol 4 (4) ◽  
pp. 652-657 ◽  
Author(s):  
Péter Bana ◽  
Áron Szigetvári ◽  
János Kóti ◽  
János Éles ◽  
István Greiner
Keyword(s):  
Continuous Flow ◽  
Drug Substance ◽  
Flow Synthesis ◽  
Continuous Preparation

The first integrated continuous-flow synthesis of the drug substance flibanserin was developed, using an uninterrupted four-step sequence, via an unprecedented route.

New approach for induction of alkyl moiety to aliphatic amines by NaBH(OAc)3 with carboxylic acid

2020 ◽  
Vol 61 (22) ◽  
pp. 151919
Author(s):  
Satoru Tamura ◽  
Aoi Sugawara ◽  
Erika Sato ◽  
Fuka Sato ◽  
Keigo Sato ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Aliphatic Amines ◽  
New Approach ◽  
Alkyl Moiety

tert-Butyl(3-cyano-4,6-dimethylpyridin-2-yl)carbonate as a green and chemoselective N-tert-butoxycarbonylation reagent

2019 ◽  
Vol 43 (17) ◽  
pp. 6549-6554
Author(s):  
Fangyu Du ◽  
Qifan Zhou ◽  
Yang Fu ◽  
Hanqi Zhao ◽  
Yuanguang Chen ◽  
...  
Keyword(s):  
Aliphatic Amines ◽  
Tert Butyl ◽  
Aromatic And Aliphatic Amines

The use of tert-butyl(3-cyano-4,6-dimethylpyridin-2yl) carbonate as a chemoselective tert-butoxycarbonylation reagent for aromatic and aliphatic amines has been demonstrated (30 examples).

scholarly journals Optimization and Scale-Up of the Continuous Flow Acetylation and Nitration of 4-Fluoro-2-methoxyaniline to Prepare a Key Building Block of Osimertinib

2020 ◽  
Vol 24 (10) ◽  
pp. 2217-2227
Author(s):  
Manuel Köckinger ◽  
Benjamin Wyler ◽  
Christof Aellig ◽  
Dominique M. Roberge ◽  
Christopher A. Hone ◽  
...  
Keyword(s):  
Building Block ◽  
Continuous Flow ◽  
Scale Up
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