Sari Deketelaere, Stefan Desimpel, Reinout Van Kerrebroeck, Lander Delputte, Emma Vandenheede, Matthias D’hooghe, Christian V. Stevens
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引用次数: 0
Abstract
The development of continuous flow processes for the Staudinger synthesis of β-lactams was investigated in order to provide an alternative to cumbersome batch procedures. First, a model reaction based on acetoxyacetyl chloride and N-(phenylmethylidene)isopropylamine was selected for initial parameter evaluation and optimization. Assessment of a broad set of bases showed that the use of diisopropylethylamine, N-methylpiperidine or tributylamine in acetonitrile is recommended for obtaining the desired 3-acetoxy-1-isopropyl-4-phenyl-β-lactam in high cis diastereoselectivity. Next, the optimized reaction set-up was successfully translated to the continuous flow production of a set of differently substituted β-lactams which are known to be difficult to prepare via batch procedures. Interestingly, an unexpected base-induced diastereoselectivity was observed during this study, allowing for tuning of the reaction conditions to favor the formation of either the cis or the trans isomer in select cases.
期刊介绍：
The main focus of the journal is flow chemistry in inorganic, organic, analytical and process chemistry in the academic research as well as in applied research and development in the pharmaceutical, agrochemical, fine-chemical, petro- chemical, fragrance industry.
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