Kilogram scale synthesis of a Linezolid analogue intermediate via tandem N-arylation and nitro group reduction in a Phoenix™ II. professional continuous flow reactor system

The morpholine ring bears utmost importance in synthetic chemistry and drug design1, since it can be found in numerous bioactive compounds. Analgesics Phenadoxone and Dextromoramide, antihypertensive Timolol, antidepressants Moclobemide and Reboxetine, antibiotics Linezolid and Finafloxacin, as well as the anticancer drug Gefitinib are all FDA approved drugs that contain a morpholine moiety. Using morpholine itself as a nucleophile is one of the most important techniques in the synthesis of such compounds. In this work, we present a large scale, two-step tandem technique for the synthesis of a Linezolid analogue key intermediate via the N-arylation of morpholine followed by a nitro group reduction2, in a flow reactor system that conveniently fits inside a single fume hood.