ArticleChemical science2017
Mass spectrometric directed system for the continuous-flow synthesis and purification of diphenhydramine.
Article in Chemical science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Integrating an Organocatalyst into a Polymeric Gel Framework for the Continuous Microflow Baylis-Hillman Reaction.ACS omega · 2026Article
- Continuous Flow Bioconjugations of NIR-AZA Fluorophores via Strained Alkyne Cycloadditions with Intra-Chip Fluorogenic Monitoring.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries.Beilstein journal of organic chemistry · 2021Review
- The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology.Journal of medicinal chemistry · 2020Review
- High-Throughput Experimentation and Continuous Flow Evaluation of Nucleophilic Aromatic Substitution Reactions.ACS combinatorial science · 2020Article
- High Throughput Experimentation Using DESI-MS to Guide Continuous-Flow Synthesis.Scientific reports · 2019Article
- Reactive Laser Ablation Electrospray Ionization Time-Resolved Mass Spectrometry of Click Reactions.Analytical chemistry · 2018Article
- A Mass Spectrometer in Every Fume Hood.Journal of the American Society for Mass Spectrometry · 2018Article
- High throughput reaction screening using desorption electrospray ionization mass spectrometry.Chemical science · 2018Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A highly integrated approach to the development of a process for the continuous synthesis and purification of diphenhydramine is reported. Mass spectrometry (MS) is utilized throughout the system for on-line reaction monitoring, off-line yield quantitation, and as a reaction screening module that exploits reaction acceleration in charged microdroplets for high throughput route screening. This effort has enabled the discovery and optimization of multiple routes to diphenhydramine in glass microreactors using MS as a process analytical tool (PAT). The ability to rapidly screen conditions in charged microdroplets was used to guide optimization of the process in a microfluidic reactor. A quantitative MS method was developed and used to measure the reaction kinetics. Integration of the continuous-flow reactor/on-line MS methodology with a miniaturized crystallization platform for continuous reaction monitoring and controlled crystallization of diphenhydramine was also achieved. Our findings suggest a robust approach for the continuous manufacture of pharmaceutical drug products, exemplified in the particular case of diphenhydramine, and optimized for efficiency and crystal size, and guided by real-time analytics to produce the agent in a form that is readily adapted to continuous synthesis.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.