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Facile Synthesis of N-protected Amino Acid Esters Assisted by Microwave Irradiation

  • Suode Zhang
  • Per I. ArvidssonEmail author
Article

Abstract

A highly efficient and safe methodology for synthesis of various N-protected amino acid ethyl esters have been established in this study. This methodology employs orthoesters as both esterification reagent and solvent for protected amino acids. The reactions were carried out under microwave irradiation in neutral conditions for only 2 min, resulting in highly pure crude products in most cases. This strategy works with a variety of N-protecting groups, such as acid labile protecting group: BOC and tBu; base labile protecting group: Fmoc; hydrogenation labile protecting group: Z and Na/NH3 labile protecting group: Tos, thus providing facile access to numerous valuable building blocks for solid phase synthesis. Further reduction of the crude protected amino acid ethyl ester by sodium borohydride under mild conditions led to the corresponding protected β-amino alcohols with excellent yield, as demonstrated by three examples.

Keywords

Amino acid ester Microwave synthesis Amino alcohol 

Notes

Acknowledgments

This work was supported by Vetenskapsrådet (The Swedish Research Council) and the Wenner-Gren Foundation. S. Zhang—Postdoctoral fellow (2003–2004) financed by The Wenner-Gren Foundation.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Howard Florey InstituteUniversity of MelbourneParkvilleAustralia
  2. 2.Department of Biochemistry and Organic ChemistryUppsala UniversityUppsalaSweden
  3. 3.Medicinal Chemistry, Discovery CNS & Pain ControlAstraZeneca R&D SödertäljeSodertaljeSweden

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