the multistep synthesis of fexofenadine
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DESCRIPTIONChem 213H: Organic Chemistry Lab Department of Chemistry, Pennsylvania State University Dr. Masters & Anthony Nocket Christopher Mallis , Leon Lin, Kayla Shellhammer. Reaction 1 Synthesis of gem -dimethyl ester 9 via successive bis -alkylation of 8 Reaction 2 - PowerPoint PPT Presentation
The Multistep Synthesis of Fexofenadine
Reaction 1Synthesis of gem-dimethyl ester 9 via successive bis-alkylation of 8
Reaction 2Synthesis of benzylic bromide 10 via Wohl-Ziegler Bromination of 9
Reaction 3Synthesis of ester aldehyde 7 via Sommelet Oxidation of 10
The Multistep Synthesis of FexofenadineChem 213H: Organic Chemistry LabDepartment of Chemistry, Pennsylvania State UniversityDr. Masters & Anthony NocketChristopher Mallis, Leon Lin, Kayla ShellhammerBackgroundFexofenadine is an anti-histamine drug used to treat allergy symptoms. It works by blocking the H1 histamine receptor. Fexofenadine is the active ingredient in Allegra. The objective for this project was to perform a multistep synthesis of fexofenadine.
www.sigmaaldrich.comRetrosynthetic Scheme for Fexofenadine Synthesis
Scheme 1Scheme 2
Scheme 3Synthetic Route
Scheme 5Scheme 6
Scheme 7bis -alkylationSommelet
Reaction 4Synthesis of alcohol 5 via Grignard addition of 6 to 7
Reaction 5Synthesis of lactol 3a via acid-catalyzed transacetalization of 5
ConclusionThis synthetic pathway was successful until the Grignard addition. Starting from 8, 9 was synthesized with a 52% yield. Using 9, 10 was synthesized with a 78% yield. Ester aldehyde 7 was synthesized with a 10% yield. A Grignard addition was then performed on 7, but it did not yield a pure product. Overall, the synthesis was fairly successful, and with more time Fexofenadine probably could have been successfully synthesized.
AcknowledgementsThe authors would like to acknowledge Penn State University for the use of their lab and materials. The authors would also like to acknowledge Katherine Masters and Anthony Nocket for their assistance in the lab.
Referencesinter alia: (a) Kawai, S. H.; Hambalek, R. J.; Just, G. J. Org. Chem. 1994, 59, 2620-2622. (b) Ronggeng, W.; Yougui, Z.; Guancho, Z. Res. Chem. Intermed. 2012. (c) Raghavendra, G. M.; Harsha, K. B.; Vinaya, K.; Mantelingu, K.; Rangappa, K. S. Synth. Commun. 2011, 41, 2296-2303. Huang, J.; Wang, W.; Wang, L.-X. Org. Proc. Res. Dev. 2010, 14, 1464-1468.(a) Fang, Q. K.; Senanayake, C. H.; Wilkinson, H. C.; Wald, S. A.; Li, H. Tetrahedron Lett. 1998, 39, 2701-2704. (b) Yu, S.; Tang, L-H; Tao, L.; Qin, X-F. Chin. J. Pharm. 2006, 37, 439-440.Masters, K.M. Chem 213H Lab Guide, Spring 2013 Edition.