期刊
ORGANIC LETTERS
卷 19, 期 4, 页码 786-789出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.orglett.6b03753
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资金
- Novartis Continuous Manufacturing Unit
A simple and robust procedure for the synthesis and use of thermally unstable dichloromethyllithium in continuous flow mode is described. By utilizing residence times in the range of milliseconds for the generation and electrophilic quench of dichloromethyllithium, the straightforward synthesis of dichlorocarbinols and benzylic pinacol esters was realized at reaction temperatures of -30 degrees C, whereas typical temperatures in traditional batch mode are below, -78 degrees C. The excellent purity profile obtained from the flow process allows us to directly telescope the exiting flow stream into semibatch quenches for further modifications. All transformations gave the desired products in remarkable purity and yield on gram scale with no need for chromatography.
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