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Synthesis of a Key Intermediate towards the Preparation of Efavirenz Using n-Butyllithium

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Abstract

A key reaction in one of the routes to efavirenz, an essential drug used in the treatment of acquired immunodeficiency syndrome (AIDS), is the ortho-lithiation reaction of N-Boc-4-chloroaniline. For the first time, we demonstrate that the reaction may be conducted using n-BuLi and show that the reaction may be performed in a flow reactor with a significantly higher yield (70%) compared to batch (28%) when using n-BuLi for the ortho-metalation reaction at a temperature of −45 °C. In addition, it was shown that tetramethylethylenediamine (TMEDA) did not need to be added to the flow reaction, which simplified the purification procedure.

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Authors and Affiliations

  1. Nelson Mandela Metropolitan University, University Way, Port Elizabeth, 6031, South Africa

    Sravanthi Chada, Devender Mandala & Paul Watts

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  1. Sravanthi Chada
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  2. Devender Mandala
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  3. Paul Watts
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Correspondence to Paul Watts.

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Chada, S., Mandala, D. & Watts, P. Synthesis of a Key Intermediate towards the Preparation of Efavirenz Using n-Butyllithium. J Flow Chem 7, 37–40 (2017). https://doi.org/10.1556/1846.2017.00008

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  • DOI: https://doi.org/10.1556/1846.2017.00008

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