Method for preparing N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine)ferrocenyl]ethylamine by microreactor

Abstract

The invention discloses a method for preparing N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine)ferrocenyl]ethylamine by a continuous flow microchannel reactor. The method comprises the following steps that an organic solvent solution of N,N-dimethyl-(R)-1-[(S)-2-ferrocenyl]ethylamine and an n-hexane solution of n-butyllithium are respectively introduced into a microchannel reactor constant temperature module by a metering pump for constant temperature treatment; then, the solutions enter a first mixing module for reaction; after the reaction is completed, the mixed solution enters a second mixingmodule to react with chlorodiphenylphosphine; acidification, extraction, drying and distillation are performed to obtain a crude product of the product of N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine)ferrocenyl]ethylamine; the crude product is subjected to alcohol recrystallization to obtain the product of N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine)ferrocenyl]ethylamine. The method has the advantages that the operation is simple, convenient and safe; the yield is high.

Description

technical field [0001] The invention relates to the field of synthesis of chiral organic small molecule catalysts, in particular to the preparation of N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine) in a continuous flow microchannel reactor Ferrocenyl]ethylamine method. Background technique [0002] Chiral phosphine ligands such as Xyliphos, Josiphos, and TriFer with a ferrocene skeleton are widely used in the field of asymmetric catalytic hydrogenation (J.Am.Chem.Soc.2004,126,9918.; Angew.Chem.Int. Ed.2007, 46, 4141), especially Xyliphos, a high-efficiency ligand, gave a conversion number of 2 million in the imine hydrogenation reaction, and the ee value of the hydrogenated product was 79%. It has been successfully applied to the chiral herbicide Jindu The industrial production of Er (Xie Jianhua; Zhou Qilin.A ctaChim.Sinica 2012,70,1427—1438); N,N-dimethyl-(R)-1-[(S)-2-(diphenylphosphine) di Ferrocenyl]ethylamine is an important intermediate in the synthesis of such chiral...

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Problems solved by technology

[0005] This method is operated in a traditional glass reactor. When n-butyllithium is added dropwise, nitrogen protection is required, and the system will heat up significantly. It is necessary to control the dropping rate all the time to keep the system temperature at about 10°C. The reaction operation process is complicated and the overall reaction The time is more than 8 hours, and by-products are formed, and the product yield is only about 65%.

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