op5b00322_si_001.pdf (127 kB)
Thermal Overman Rearrangement of a Glucal Derivative in a Tube Reactor on Pilot Plant Scale
journal contribution
posted on 2016-01-06, 00:00 authored by Franz Amann, Michael Frank, Robert Rhodes, Andrew Robinson, Martin Kesselgruber, Stefan AbeleThe 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.