Development of an Organometallic Flow Chemistry Reaction at PilotPlant Scale for the Manufacture of Verubecestat
Contributor(s):: Thaisrivongs, David A., Naber, John R., Rogus, Nicholas J., Spencer, Glenn
We report the development of an organolithium addition to a chiral ketimine at pilot-plant scale using flow chemistry. Given the mixing sensitivity of this process, established previously at both lab and kilogram scale, we conducted critical experiments to understand the impact of flow rate,...
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...