Process Development for the Synthesis of Monocyclic β-Lactam Core 17
| Autor: | David C. Boyles, Jianmin Sun, Joel T. Arcari, Matthew Frank Brown, Yong Tao, Susan C. Lilley, Jeremy T. Starr, Manjinder S. Lall, Andrew Morgan Stewart, Mark J. Mitton-Fry, David B. Damon |
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| Rok vydání: | 2018 |
| Předmět: |
010405 organic chemistry
Organic Chemistry Imine Ketene 010402 general chemistry 01 natural sciences Combinatorial chemistry Cycloaddition 0104 chemical sciences chemistry.chemical_compound chemistry Yield (chemistry) Lactam Amine gas treating Physical and Theoretical Chemistry Enantiomer Enantiomeric excess |
| Zdroj: | Organic Process Research & Development. 22:212-218 |
| ISSN: | 1520-586X 1083-6160 |
| DOI: | 10.1021/acs.oprd.7b00359 |
| Popis: | Process development and multikilogram synthesis of the monocyclic β-lactam core 17 for a novel pyridone-conjugated monobactam antibiotic is described. Starting with commercially available 2-(2,2-diethoxyethyl)isoindoline-1,3-dione, the five-step synthesis features several telescoped operations and direct isolations to provide significant improvement in throughput and reduced solvent usage over initial scale-up campaigns. A particular highlight in this effort includes the development of an efficient Staudinger ketene–imine [2 + 2] cycloaddition reaction of N-Boc-glycine ketene 12 and imine 9 to form racemic β-lactam 13 in good isolated yield (66%) and purity (97%). Another key feature in the synthesis involves a classical resolution of racemic amine 15 to afford single enantiomer salt 17 in excellent isolated yield (45%) with high enantiomeric excess (98%). |
| Databáze: | OpenAIRE |
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