A new synthetic route for Valsartan via a novel Decarboxylative Biaryl Synthesis
نویسنده
چکیده
Literature and Further Reading (see also www.chemie.uni-kl.de/goossen) [1] U.S. Department of Health and Human Services; National Heart, Lung, and Blood, Institute; National High Blood Pressure Education Program, NIH Publication No. 03 – 5233, December 2003. [2] D. Carini, J. Duncia, P. Aldrich, A. Chiu, A. Johnson, M. Pierce, W. Price, J. Santella III, G. Wells, R. Wexler, P. Wong, S. E. Yoo, P. Timmermans, J. Med. Chem. 1991, 34, 2525-2547. [3] For sales figures, see: Novartis Annual Report 2006, Novartis International AG, Basel (2007). [4] For published syntheses, see: a) P. Bühlmayer, F. Ostermayer, T. Schmidlin, Eur. Pat. Appl. EP443983, 1991; b) P. Bühlmayer, P. Furet, L.Ciscione, M. de Gasparo, S. Whitebread, T. Schmidlin, R. Lattmann, J. Wood, J. Bioorg. Med. Chem. Lett. 1994, 4, 29-34. [5] For state-of-the-art Suzuki couplings, see: a) A. F. Littke, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41, 4176-4211; b) J. Kristensen, M. Lysén, P. Vedsø, M .Begtrup, Org. Lett. 2001, 3, 1435-1437. [6] a) L. J. Gooßen, G. Deng, L. M. Levy, Science 2006, 313, 662-664; b) L. J. Gooßen, N. Rodríguez, B. Melzer, C. Linder, G. Deng, L. M. Levy, J. Am. Chem. Soc. 2007, 12, 4824-4833; c) L. J. Gooßen, W. R. Thiel, N. Rodríguez, C. Linder, B. Melzer, Adv. Synth. Catal., in press (2007). [7] L. J. Gooßen, B. Melzer, J. Org. Chem. 2007, 72, 7473-7476. Abstract : A new catalytic system composed of copper and palladium has been recently reported by our group for the decarboxylation of aromatic carboxylates and the cross-coupling of the resulting aryl metal species with aryl halides. Already at its current state of development, this biaryl synthesis has opened up new opportunities for the industrial synthesis of high-value pharmaceutical intermediates, such as the Sartans or Boscalid analogs. Herein, we present the synthesis of Valsartan as one example of the many possible applications of the novel decarboxylative coupling in the synthesis of bioactive molecules. Our proposed synthetic route not only promises to be more environmentally benign, but also significantly cheaper in comparison to the literature synthesis. Bettina Zimmermann geb. Melzer, Lukas J. Gooßen*
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