Scale-up Synthesis of (R)- and (S)-N-(2-Benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide Hydrochloride, A Versatile Reagent for the Preparation of Tailor-Made α- and β-Amino Acids in an Enantiomerically Pure Form
- Todd T. Romoff
- ,
- Andrew B. Palmer
- ,
- Noel Mansour
- ,
- Christopher J. Creighton
- ,
- Toshio Miwa
- ,
- Yuki Ejima
- ,
- Hiroki Moriwaki
- , and
- Vadim A. Soloshonok
Abstract
Unusual amino acids are of crucial importance to the synthesis of bioactive peptides and new chemical entities. Innovative methodology is always needed for the preparation of enantiomerically pure amino acids that does not rely on tedious resolution procedures. The proline-derived ligands (R)- and (S)-N-(2-benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide are outstanding, versatile, and recyclable reagents for the synthesis of tailor-made α- and β-amino acids. Here we report initial studies of the scale-up synthesis of the HCl salt of these reagents on the 100 g scale. The results demonstrate an increased efficiency and environmental friendliness of the bench-scale procedure and provides a firm foundation for the manufacture on multikilogram and larger scales.
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