10.1021/acs.oprd.5b00322.s001 Franz Amann Franz Amann Michael Frank Michael Frank Robert Rhodes Robert Rhodes Andrew Robinson Andrew Robinson Martin Kesselgruber Martin Kesselgruber Stefan Abele Stefan Abele Thermal Overman Rearrangement of a Glucal Derivative in a Tube Reactor on Pilot Plant Scale American Chemical Society 2016 95 kg trichloroacetamide 4 Actelion Pharmaceuticals Ltd Tube Reactor multikilogram scale 4. API Glucal Thermal Overman Rearrangement compounds 3 problem Trichloroacetimidate 4 flow chemistry process Overman rearrangement Pilot Plant ScaleThe development instability batch mode procedure 2016-01-06 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Thermal_Overman_Rearrangement_of_a_Glucal_Derivative_in_a_Tube_Reactor_on_Pilot_Plant_Scale/2091160 The development of a continuous process for the thermal Overman rearrangement of <i>O</i>-[(2<i>R</i>,3<i>S</i>)-2-(<i>tert</i>-butyldimethylsilyloxymethyl)-3,6-dihydro-2<i>H</i>-pyran-3-yl]-trichloro-ethanecarboximidate <b>3</b> to the corresponding trichloroacetamide <b>4</b> is described. Trichloroacetimidate <b>4</b> is an intermediate for an active pharmaceutical intermediate (API) under development at Actelion Pharmaceuticals Ltd. The instability of compounds <b>3</b> and <b>4</b> 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 <b>4</b>.