Thermal Overman Rearrangement of a Glucal Derivative in a Tube Reactor on Pilot Plant Scale

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• 作者：Franz Amann ; Michael Frank ; Robert Rhodes ; Andrew Robinson ; Martin Kesselgruber ; Stefan Abele
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：February 19, 2016
• 年：2016
• 卷：20
• 期：2
• 页码：446-451
• 全文大小：279K
• ISSN：1520-586X

文摘

The development of a continuous process for the thermal Overman rearrangement of O-[(2R,3S)-2-(tert-butyldimethylsilyloxymethyl)-3,6-dihydro-2H-pyran-3-yl]-trichloro-ethanecarboximidate 3 to the corresponding trichloroacetamide 4 is described. Trichloroacetimidate 4 is an intermediate for an active pharmaceutical intermediate (API) under development at Actelion Pharmaceuticals Ltd. The instability of compounds 3 and 4 at temperatures above 100 °C prevented scale-up of the original batch mode procedure to the required multikilogram scale. This problem was solved by developing a flow chemistry process used for the successful production of 95 kg of 4.