期刊
ORGANIC PROCESS RESEARCH & DEVELOPMENT
卷 20, 期 10, 页码 1833-1837出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.6b00281
关键词
continuous manufacturing; organolithium chemistry; aryl boronic acids; scale-up concept
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.
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