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Issue 7, 2013
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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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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.

Graphical abstract: 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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Publication details

The article was received on 29 Mar 2013, accepted on 14 May 2013 and first published on 21 May 2013


Article type: Edge Article
DOI: 10.1039/C3SC50859E
Citation: Chem. Sci., 2013,4, 2822-2827
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    End-to-end continuous flow synthesis and purification of diphenhydramine hydrochloride featuring atom economy, in-line separation, and flow of molten ammonium salts

    D. R. Snead and T. F. Jamison, Chem. Sci., 2013, 4, 2822
    DOI: 10.1039/C3SC50859E

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