Match-Making Reactors to Chemistry: A Continuous Manufacturing-Enabled Sequence to a Key Benzoxazole Pharmaceutical Intermediate
Contributor(s):: Yayla, Hatice G., Peng, Feng, Mangion, Ian K., McLaughlin, Mark, Campeau, Louis-Charles, Davies, Ian W.DiRocco, Daniel A., Knowles, Robert R.
The focus of this study was to develop a chemical reaction sequence toward a key benzoxazole building block, required for clinical manufacturing of a lead candidate in the respiratory disease area. The chemistry consisted of initial low-temperature reactions with an organometallic reagent to...
Using Flow To Outpace Fast Proton Transfer in an Organometallic Reaction for the Manufacture of Verubecestat (MK-8931)
Contributor(s):: Thaisrivongs, David A., Naber, John R., McMullen, Jonathan P.
We report that an organolithium addition to a chiral ketimine, which because of competitive proton transfer proceeds with only modest yield in batch, can be significantly improved in flow. The transformation was discovered to be highly mixing-sensitive but remarkably temperature-independent in...
The Synthesis of Bromomethyltrifluoroborates through Continuous Flow Chemistry
Contributor(s):: Broom, Toby, Hughes, Mark, Szczepankiewicz, Bruce G., Ace, Karl, Hagger, Ben, Lacking, Gary, Chima, Ranjit, Marchbank, Graeme, Alford, Gareth, Evans, Paul, Cunningham, Christopher, Roberts, John C., Perni, Robert B., Berry, Malcolm, Rutter, Andrew, Watson, Simon A
A continuous flow process was developed for the synthesis of potassium bromomethyltrifluoroborate, a key precursor for Suzuki–Miyaura coupling reagents. The continuous flow process was used to produce potassium bromomethyltrifluoroborate on scales from grams to kilograms, and the successful...