Book of abstracts version 5

A three step synthesis to a β-lactam antibiotic drug
Author
ynthesis to a β-lactam antibiotic drug
Floran Hüpscher
Academy of Technology for Health and Environment
Avans Hogeschool, Breda
Paula Contreras Carballada
Abstract
In this study, the β-lactam antibiotic drug 2-Azetidinecarboxylic acid, 4-oxo-1-(phenylmethyl)-, ethyl ester (structure
shown in the bottom right in figure 1) is synthesized using the commercially available chemicals ethyl glyoxylate, N -
benzylhydroxylamine, trimethylsilylacetylene and cesium fluoride in a three step synthesis. In th e synthesis step, requiring
a source of fluorine, TBAF (Tetra-n-butylammoniumfluoride) was used in literature but resulted in a low yield (a maximum
of 31% was acquired)[1]. The low yield is possibly the result of the 5% water content in commercial TBAF so lutions[2]
The aim of this study is to investigate the effect of using an anhydrous source of fluorine (cesium fluoride instead of TBAF)
on the yield of the respective synthesis step. It is expected that the yield will be higher than 36%. The intermediate
structure needed to synthesize the desired β-lactam product is synthesized using reflux apparatuses and is purified using
column chromatography. This two-step synthesis of the intermediate is depicted in figure 1. The third and final step in the
synthesis is a 96-hour reflux reaction using cesium fluoride as fluorine source. The reaction will be monitored using TLC
and purified using column chromatography. The intermediates and the product are analyzed using FTIR and H -NMR
spectroscopy.
Keywords: β-lactam, trimethylsilyl group removal, cesium fluoride.
Table of content
Figure 1: The three step reaction path to synthesize β-lactam structure.
[1] Chuljin. A. e. al., „A New Approach to the Synthesis of Monocyclic / beta-Lactam derivatives,” Journal of Organic
Chemistry, vol. 59, nr. 21, pp. 6282-6286, 1994.
[2] P. C. Carballada, „Untersuchung zur Darstellung von 5 -trimethylsilyl-substitulerten Isoxazolinen und deren Spaltung zu
beta-Lactamen,” unpublished results, Berlin, 2003.
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