Kilogram-level amplification-scale production chiral biguanide catalyst synthesis method

Abstract

The invention discloses a kilogram-level amplification-scale production chiral biguanide catalyst synthesis method, which comprises: S1, carrying out an amine alkylation reaction by using chiral ethylenediamine and benzyl bromide as raw materials to obtain chiral bis-secondary amine; s2, adding a solvent and thiophosgene into the same kettle, carrying out a thiocarbonylation reaction to obtain chiral thiourea, and carrying out pulping purification treatment on the chiral thiourea; s3, adding oxalyl chloride into the same kettle, and performing reflux reaction in a solvent to obtain chiral 2-chloroimidazoline onium salt; and s4, evaporating out the solvent in the step S3 from the original kettle, then adding piperazine into the same kettle, and carrying out amination coupling reaction to obtain a chiral biguanide salt ion pair catalyst BG-I; and according to the synthesis method, one-kettle multi-step same-kettle feeding is adopted, the production stability and safety are improved, the synthesis route is shortened, meanwhile, the traditional tedious pulping purification process is simplified, the synthesis efficiency is improved, the synthesis cost is reduced, and the method is stable in process and suitable for industrial large-scale production.

Description

technical field [0001] The invention relates to the field of production of chiral biguanide phase-transfer catalysts, in particular to a synthesis method capable of producing chiral biguanide catalysts on a kilogram scale. Background technique [0002] Chiral biguanide salt ion-pair phase transfer catalyst (BG-I) is widely used in various asymmetric catalysis fields, and has great application potential in the fields of organic synthesis and biomedicine, especially for the development of high value-added chiral intermediates and Drugs have great help, such as: asymmetric thioether oxidation reaction (Nat.Commun., 2016, 7, 13455), asymmetric dihydroxylation reaction and carbon-based hydroxylation reaction (J.Am.Chem.Soc., 2015,137,10677), asymmetric alkylation reaction (J.Am.Chem.Soc.,2016,138,9935) and the preparation of neurological drug Armodafinil (Nat.Commun.,2016,7, 13455). E.g figure 1 Shown in: BG-I-catalyzed asymmetric thioether oxidation for the synthesis of armod...

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Problems solved by technology

[0004] The purpose of the present invention is to overcome the above-mentioned defects in the prior art, to provide a kind of synthetic method that can produce chiral biguanide catalyst on a large scale at the kilogram level, which mainly solves the high cost and low efficiency existing in the existing BG-I synthetic method , complex operation, inability to scale up, and technical problems that are not suitable for industrial production

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