Ah, back to my old thiolactam days, when I would utilize and Rapaport protocol to extend a pyrrolidine or piperidine out. So I thought this has to be a reaction that has been reduced in a continuous flow manner — low and behold, someone has used this sequence in functionalizing pyrimidines (Beilstein JOC 2011)……..are my med chem colleagues in the house?
As a starting point if you haven’t ever performed these reactions, a scheme for the secondary lactam transformation is shown below and the subst version just below that.
Using this concept, the transformation was applied to some substituted sulfur-pyrimidines.
As part of the reaction intensification process, this group found the kinetic profile quickly to go along with the concentration for the residence time and made a small library of compounds (see paper for how the kinetic studies were performed). The tables below indicate the materials to start and corresponding final compounds and their yields.
The coiled capillary reactor design is shown for the control of temperature and flow. Happy Reading!