CHIMIA (May 2003)

Automated Parallel Synthesis of N-Alkylated-?-Amino Methyl Esters in Gram Quantities

  • Sylvie Chamoin,
  • Hans-Jörg Roth,
  • Carsten Borek,
  • Aline Jary,
  • Hugues Maillot

DOI
https://doi.org/10.2533/000942903777679370
Journal volume & issue
Vol. 57, no. 5

Abstract

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N-alkylated-?-amino acids and methyl esters are a special class of building blocks used for the production of combinatorial libraries. They have two reactive groups for their incorporation into chemical scaffolds and they bear on their 3-atom backbone two residues which contribute to the diversity of a library. The work contained herein describes the methodology to synthesize N-alkylated-?-amino acids and methyl esters in a parallel and automated fashion. The aim was the preparation of a series of these building blocks in gram quantities. Furthermore, the reported method tolerates that the N-residues as well as the ?-C residues bear a wide range of pharmacologically relevant functional groups, including ones with acid-labile protecting groups. Following a reductive alkylation procedure, using NaBH4 as reducing reagent, 14 different ?-amino methyl esters have been combined with nine different aldehydes. The products were isolated in satisfying purities and moderate to good yields. For the demanding extraction procedure (volumes of 150 ml), a recently developed automated system has been successfully applied and is reported here for the first time.

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