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

被引：46

作者：

Hafner, Andreas ^{[1
]}

Filipponi, Paolo ^{[1
]}

Piccioni, Lorenzo ^{[1
]}

Meisenbach, Mark ^{[1
]}

Schenkel, Berthold ^{[1
]}

Venturoni, Francesco ^{[1
]}

Sedelmeier, Joerg ^{[1
]}

机构：

[1] Novartis Pharma AG, Fabrikstr 14, CH-4002 Basel, Switzerland

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2016年 / 20卷 / 10期

关键词：

continuous manufacturing; organolithium chemistry; aryl boronic acids; scale-up concept; FLASH CHEMISTRY; SYSTEM; BATCH; ACIDS; TEMPERATURES; ARYLLITHIUMS; INTEGRATION; GENERATION; REACTOR;

D O I：

10.1021/acs.oprd.6b00281

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

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.

引用

页码：1833 / 1837

页数：5

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