End-to-end continuous flow synthesis and purification of diphenhydramine hydrochloride featuring atom economy, in-line separation, and flow of molten ammonium salts
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DRS TFJ (Revised) 051313 SC-EDG-03-2013-050859.pdf
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667.76 KB
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Checksum (MD5)
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Author(s)
Snead, David R.
Jamison, Timothy F.
Date Issued
May 2013
Journal
Chemical Science
Publisher
Royal Society of Chemistry
Citation
Snead, David R., and Timothy F. Jamison. “End-to-End Continuous Flow Synthesis and Purification of Diphenhydramine Hydrochloride Featuring Atom Economy, in-Line Separation, and Flow of Molten Ammonium Salts.” Chemical Science 4, no. 7 (2013): 2822.
Version
Author's final manuscript
Abstract
A continuous end-to-end synthesis and purification of diphenhydramine hydrochloride featuring atom economy and waste minimization is described. Combining a 1 : 1 molar ratio of the two starting material streams (chlorodiphenylmethane and N,N-dimethylaminoethanol) in the absence of additional solvent at high temperature gives the target compound directly as a molten salt (ionic liquid above 168 °C) in high yield. This represents the first example of continuous active pharmaceutical ingredient (API) production in this manner. Six of the twelve principles of green chemistry as defined by the American Chemical Society are achieved, most prominently waste minimization and atom economy.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1039/c3sc50859e
