Synfacts 2006(5): 0527-0527  
DOI: 10.1055/s-2006-934406
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

Solid-Phase Synthesis of Hindered Amides

Contributor(s): Yasuhiro Uozumi, Masahiro Kimura
M. J. Liley*, T. Johnson, S. E. Gibson
Medivir UK Ltd., Little Chesterford and Imperial College London, UK
Further Information

Publication History

Publication Date:
21 April 2006 (online)

Significance

The solid-phase synthesis of hindered amides was demonstrated using the aldehyde dual-linker [5-(4-formyl-3-hydroxyphenoxy)-pentanoic acid and Sieber amide] system. Thus, the secondary amine 2 was prepared by reductive alkylation of valine-OMe with Sieber amide resin-bound aldehyde 1 using NaBH3CN followed by deprotection of the allyl group with Pd(PPh3)4 and PhSiH3. Acylation of the secondary amine with Z-Leu-OH was performed via O to N acyl transfer using HBTU, HOBt, and N-methylmorpholine (NMM), and the subsequent cleavage from the resin by TFA gave sterically hindered amide 3. The conversion was determined by HPLC analysis to be 95%.