Flow microreactor synthesis of disubstituted pyridines from dibromopyridines via Br/Li exchange without using cryogenic conditions

A flow microreactor method for the synthesis of disubstituted pyridines by generation of pyridyllithiums followed by reactions with electrophiles has been developed. By using a short residence time and efficient temperature control, the cryogenic conditions required for conventional batch macro processes can be avoided. Sequential introduction of two different electrophiles into dibromopyridines has been achieved using an integrated flow microreactor system composed of four micromixers and four microtube reactors, to obtain disubstituted pyridine compounds.