Multistep Flow Synthesis of Diazepam Guided by Droplet-Accelerated Reaction Screening with Mechanistic Insights from Rapid Mass Spectrometry Analysis
| Autor: | Michael Wleklinski, David H. Thompson, H. Samuel Ewan, R. Graham Cooks, Kiran Iyer, Seok-Hee Hyun |
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| Rok vydání: | 2017 |
| Předmět: |
Electrospray
Chromatography 010405 organic chemistry Organic Chemistry Microfluidics Analytical chemistry 010402 general chemistry Mass spectrometry 01 natural sciences Leidenfrost effect 0104 chemical sciences Solvent chemistry.chemical_compound chemistry Benzophenone Physical and Theoretical Chemistry Analysis method |
| Zdroj: | Organic Process Research & Development. 21:1566-1570 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.7b00218 |
| Popis: | Electrospray and Leidenfrost droplet accelerated reactions were used as a predictive tool for estimating the outcome of microfluidic synthesis as demonstrated by Wleklinski et al. Rapid analysis by electrospray-mass spectrometry (ESI-MS) also provided immediate feedback on reaction outcomes in flow reactions. Significant reaction acceleration was observed in electrospray relative to the corresponding bulk reaction. This rapid reaction screening and analysis method has allowed for the detection of previously unreported outcomes in the reaction between 5-chloro-2-(methylamino)benzophenone and haloacetyl chloride (halo = Cl or Br) in the continuous synthesis of diazepam. In our current study, a more detailed extension of the previous work, we report acceleration factors that are solvent dependent; additional byproducts that were observed on the microfluidic scale that were absent in the droplet reactions. Gaining insight from this combined droplet and microfluidic screening/rapid ESI-MS analysis approach, we... |
| Databáze: | OpenAIRE |
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