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Synthesis of Fexofenadine via Rhodium-Catalyzed Hydroaminomethylation

Abstract

Rhodium-catalyzed hydroaminomethylation is employed in a new synthesis of the anti-histamines, Terfenadine and Fexofenadine. Linear selective hydroformylation is performed using a homogeneous Rh-bisphosphite catalyst, followed by reductive amination under H2/CO. The reaction can be performed without protection of the hydroxyl substituent in the starting olefins.

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Scheme 1
Scheme 2

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Acknowledgements

The author thanks Dowpharma for support of this work. Helpful scientific discussions with Drs. Cynthia Rand, Jerzy Klosin and John Briggs of Dow Chemical are gratefully acknowledged.

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Correspondence to Gregory T. Whiteker.

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Whiteker, G.T. Synthesis of Fexofenadine via Rhodium-Catalyzed Hydroaminomethylation. Top Catal 53, 1025–1030 (2010). https://doi.org/10.1007/s11244-010-9574-9

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Keywords

  • Hydroformylation
  • Syngas
  • Carbonylation