A Simple Scale-up Strategy for Organolithium Chemistry in Flow Mode: From Feasibility to Kilogram Quantities

• DOI: 10.1021/acs.oprd.6b00281
• Publication Date: 2016-09-27T11:31:37Z
• Authors: Andreas Hafner; Paolo Filipponi; Lorenzo Piccioni; Mark Meisenbach; Berthold Schenkel; Francesco Venturoni; Joerg Sedelmeier
• Keywords: Flow chemistry; Borylation

A platform for conducting organolithium chemistry in continuous flow mode, covering the scales from medicinal to later phase process development, is described. The use of this setup, which mimics concept flash on scale, has been demonstrated by exemplary, large-scale preparation (4-fluoro-2-(trifluoromethyl)phenyl)boronic acid following a reaction sequence halogen/lithium exchange, borylation, and semibatch workup. Furthermore, key factors corresponding practical assessments required streamlined seamless scale-up lab environment higher productivity are highlighted.