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>.