Reconfiguration of a Continuous Flow Platform for Extended Operation: Application to a Cryogenic Fluorine-Directed ortho-Lithiation Reaction

被引：25

作者：

Newby, James A. ^{[1
]}

Blaylock, D. Wayne ^{[2
]}

Witt, Paul M. ^{[2
]}

Turner, Richard M. ^{[1
]}

Heider, Patrick L. ^{[2
]}

Harji, Bashir H. ^{[3
]}

Browne, Duncan L. ^{[1
]}

Ley, Steven V. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Chem, Whiffen Lab, Cambridge CB2 1EW, England

[2] Dow Chem Co USA, Midland, MI 48674 USA

[3] Brookfield Business Ctr, Cambridge Reactor Design, Unit D2, Cottenham CB24 8PS, Cambs, England

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2014年 / 18卷 / 10期

基金：

英国工程与自然科学研究理事会;

关键词：

CROSS-COUPLING REACTIONS; ORTHO-METALATION; ENABLING TECHNOLOGY; PROCESS WINDOWS; DRUG DISCOVERY; NOBEL LECTURE; CHEMISTRY; PALLADIUM; REACTORS; HETEROCYCLES;

D O I：

10.1021/op500221s

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A flow platform for preparing various aromatic scaffolds using a low-temperature fluorine-directed ortho-lithiation reaction has been successfully reconfigured to allow large-scale processing over extended reaction periods. During the course of this work several key factors have resulted in the development of new technology such as stainless steel y-piece fittings capable of hosting a thermocouple at the point of mixing which directly controls the power output of a cryogenic cooling device. These developments have enabled the continuous processing of an industrially relevant product, where adequate mixing, cooling, and exotherm control are important for successful operation. The configuration culminates in a large-scale campaign where the flow platform is utilised to process over 100 g of pure product over 7 h, in a yield of 80% after workup.

引用

页码：1221 / 1228

页数：8