Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem

Karel M J Brands; Ronald B Jobson; Karen M Conrad; J Michael Williams; Brenda Pipik; Mark Cameron; Antony J Davies; Peter G Houghton; Michael S Ashwood; Ian F Cottrell; Robert A Reamer; Derek J Kennedy; Ulf-H Dolling; Paul J Reider

doi:10.1021/jo011170c

Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem

J Org Chem. 2002 Jul 12;67(14):4771-6. doi: 10.1021/jo011170c.

Authors

Karel M J Brands¹, Ronald B Jobson, Karen M Conrad, J Michael Williams, Brenda Pipik, Mark Cameron, Antony J Davies, Peter G Houghton, Michael S Ashwood, Ian F Cottrell, Robert A Reamer, Derek J Kennedy, Ulf-H Dolling, Paul J Reider

Affiliation

¹ Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. [email protected]

PMID: 12098287
DOI: 10.1021/jo011170c

Abstract

An efficient synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio containing side chain of ertapenem (MK-0826) is described. Starting material N-(O,O-diisopropyl phosphoryl)-trans-4-hydroxy-L-proline is converted in a one-pot process to (2S)-cis-3-[[(4-mercapto-2-pyrrolidinyl)carbonyl]amino]benzoic acid monohydrochloride in 70-75% overall yield via a series of six reactions. The development of each of these reactions and the isolation of the product is discussed in detail.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Infective Agents / chemical synthesis*
Anti-Infective Agents / chemistry
Carbapenems / chemical synthesis*
Carbapenems / chemistry
Chromatography, High Pressure Liquid
Combinatorial Chemistry Techniques*
Ertapenem
Lactams*
Molecular Structure
Pyrrolidines / chemistry
Stereoisomerism
beta-Lactams

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Carbapenems
Lactams
Pyrrolidines
beta-Lactams
Ertapenem