Y. Nishino, Makoto Kobayashi, T. Shinno
Sep 24, 2003
Citations
0
Influential Citations
17
Citations
Journal
Organic Process Research & Development
Abstract
A practical large-scale process for the synthesis of doripenem hydrate (1), a novel parenteral 1β-methylcarbapenem antibiotic, from p-nitrobenzyl-protected enolphosphate 2b and N-(p-nitrobenzyloxycarbonyl)-protected aminomethylpyrrolidine 3c is described. We found effective extraction conditions to remove p-toluidine and most other organic impurities using a THF/water system containing an inorganic salt. Significant improvements have been made to the previous synthesis using a medicinal chemical procedure. The new process requires no chromatographic purification and affords the target compound 1 as a sterile crystalline powder. Several kilograms of compound 1 were successfully prepared by this process.