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A Three-Minute Synthesis and Purification of Ibuprofen: Pushing the Limits of Continuous-Flow Processing
Contributor(s):: Snead, David R., Jamison, Timothy F.
In a total residence time of three minutes, ibuprofen was assembled from its elementary building blocks with an average yield of above 90 % for each step. A scale-up of this five-stage process (3 bond-forming steps, one work-up, and one in-line liquid–liquid separation) provided ibuprofen at a...
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Enzyme synthesis of cephalexin in continuous-flow microfluidic device in ATPS environment
Contributor(s):: Vobecká, Lucie, Tichá, Linda, Atanasova, Aleksandra, Slouka, Zdeněk, Hasal, Pavel, Přibyl, Michal
We present an experimental study dealing with the transfer of the enzyme synthesis of cephalexin from a batch arrangement to a continuous-flow microfluidic system with integrated reaction product separation and enzyme recovery. Cephalexin is synthesized by penicillin acylase in a kinetic regime...
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Development and Scale-Up of Three Consecutive Continuous Reactions for Production of 6-Hydroxybuspirone
Contributor(s):: LaPorte, Thomas L., Hamedi, Mourad, DePue, Jeffrey S., Shen, Lifen, Watson, Daniel, Hsieh, Daniel
This paper describes the development of a continuous, high yielding, and scalable enolization, oxidation, and quench process for the hydroxylation of the azapirone psychtropic agent buspirone to afford 6-hydroxybuspirone...
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Application of Continuous Flow for DIBAL-H Reduction and n-BuLi Mediated Coupling Reaction in the Synthesis of Eribulin Mesylate
Contributor(s):: Fukuyama, Takashi, Chiba, Hiroyuki, Kuroda, Hirofumi, Takigawa, Teiji, Kayano, Akio, Tagami, Katsuya
Here we examined the use of continuous flow conditions for the final assembly of eribulin mesylate aimed to avoid cryogenic condition. The diisobutylaluminum hydride reduction of ester 2 to aldehyde 3 and n-butyllithium-mediated coupling of aldehyde 3 and sulfone fragment 4 to produce...
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The Use of Molecular Oxygen in Pharmaceutical Manufacturing: Is Flow the Way to Go?
Contributor(s):: Hone, CA, Roberge, DM, Kappe, CO
Molecular oxygen is arguably the greenest reagent available to the organic chemist. Most commonly, a diluted form of oxygen gas, consisting of less than 10% O-2 in N-2 ("synthetic air"), is used in pharmaceutical and fine chemical batch manufacturing to effectively address safety concerns when...
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Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source
Contributor(s):: Kockinger, M, Hone, CAGutrnann, B, Hanselmann, P, Bersier, M, Torvisco, A, Kappe, CO
The development of a scalable telescoped continuous flow procedure for difluoromethylation of a protected amino acid with fluoroform (CHF3, R-23) gas and subsequent high temperature deprotection to provide eflornithine, an important Active Pharmaceutical Ingredient (API), is described....
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Micro reactor and flow chemistry for industrial applications in drug discovery and development
Contributor(s):: Baraldi, PT, Hessel, V
In this review, case studies focused on syntheses of active pharmaceutical ingredients, intermediates and lead compounds are reported employing micro reactors and continuous flow technology in areas such as medicinal chemistry, chemical development and manufacturing. The advantages of flow...
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Improving chemical synthesis using flow reactors
Contributor(s):: Wiles, C, Watts, P
Owing to the competitive nature of the pharmaceutical industry, Research Articleers involved in lead compound generation are under continued pressure to identify and develop promising programmes of Research Article in order to secure intellectual property. The potential of a compound for...
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Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients
Contributor(s):: De;Souza, JM, Galaverna, RDe, Souza, AAN, Brocksom, TJ, Pastre, JC, De, Souza, ROMA, De;Oliveira, KT
We present a comprehensive review of the advent and impact of continuous flow chemistry with regard to the synthesis of natural products and drugs, important pharmaceutical products and definitely responsible for a revolution in modem healthcare. We detail the beginnings of modern drugs and the...
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7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
| Contributor(s):: Ziegler, RE, Desai, BKJee, JA, Gupton, BF, Roper, TD, Jamison, TF
Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5h in sequential...