A simple scale-up strategy for organolithium chemistry in flow mode: From feasibility to kilogram quantities

A Hafner, P Filipponi, L Piccioni… - … process research & …, 2016 - ACS Publications
A Hafner, P Filipponi, L Piccioni, M Meisenbach, B Schenkel, F Venturoni, J Sedelmeier
Organic process research & development, 2016ACS Publications
A platform for conducting organolithium chemistry in continuous flow mode, covering the
scales from medicinal chemistry to later phase process development, is described. The use
of this flow setup, which mimics the concept of flash chemistry on scale, has been
demonstrated by the exemplary, large-scale preparation of (4-fluoro-2-(trifluoromethyl)
phenyl) boronic acid following a reaction sequence of halogen/lithium exchange, borylation,
and semibatch workup. Furthermore, the key factors and corresponding practical …
A platform for conducting organolithium chemistry in continuous flow mode, covering the scales from medicinal chemistry to later phase process development, is described. The use of this flow setup, which mimics the concept of flash chemistry on scale, has been demonstrated by the exemplary, large-scale preparation of (4-fluoro-2-(trifluoromethyl)phenyl)boronic acid following a reaction sequence of halogen/lithium exchange, borylation, and semibatch workup. Furthermore, the key factors and corresponding practical assessments required for the streamlined and seamless scale-up from lab environment to higher productivity are highlighted.
ACS Publications
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