Method for recovering ligand in asymmetric synthesis of S-(+)-2,2-dimethyl cyclopropanecarboxylic acid

Abstract

The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for recovering a ligand in asymmetric synthesis of S-(+)-2,2-dimethyl cyclopropanecarboxylic acid. The recovery method comprises the following steps: mixing an ethyl diazoacetate solution, an oxazoline ligand, a catalyst, isobutene and a reaction solvent, and carrying out cyclopropanation to obtain an ethyl dimethylcyclopropane formate crude product; mixing the crude product, an organic solvent and inorganic alkali, hydrolyzing to obtain a hydrolysate, and removing the organic solvent of the hydrolysate to obtain a water-phase product; performing extraction and phase separation on the water-phase product to obtain an organic layer product; and mixing the organic layer product, an aprotic organic solvent, tertiary organic amine and a sulfonic acid esterification reagent, activating, purifying, and recovering to obtain the oxazoline ligand. The recovery method provided by the invention effectively solves the problem that the used ligand cannot be recovered in the existing asymmetric synthesis method of S-(+)-2, 2-dimethyl cyclopropanecarboxylic acid.

Description

technical field [0001] The application belongs to the technical field of chemical synthesis, and in particular relates to a method for recovering ligands in the asymmetric synthesis of S-(+)-2,2-dimethylcyclopropanecarboxylic acid. Background technique [0002] S-(+)-2,2-Dimethylcyclopropanecarboxylic acid, the CAS number is [14590-53-5], the molecular structure is . S-(+)-2,2-Dimethylcyclopropanecarboxylic acid is a key intermediate in the synthesis of cilastatin (a renal dehydrodipeptidase inhibitor), a compound of cilastatin and imipenem The preparation is suitable for combined infection of multiple bacteria and mixed infection of aerobic bacteria and anaerobic bacteria. The chemical synthesis methods of S-(+)-2,2-dimethylcyclopropanecarboxylic acid mainly include the following chemical resolution methods and asymmetric synthesis. [0003] Chemical resolution: first synthesize R,S-(+)-2,2-dimethylcyclopropanecarboxylic acid, and then obtain S-(+)-2,2-dimethylcycloprop...

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Problems solved by technology

[0006] In view of this, the application provides the recovery method of the ligand in the asymmetric synthesis of S-(+)-2,2-dimethylcyclopropanecarboxylic acid, the application can be obtained from S-(+)-2,2-dimethyl A method for recovering ligands in the asymmetric synthesis of cyclopropanecarboxylic acid. This recovery method has the advantages of high recovery rate, low cost and simple operation, and effectively solves the problem of existing asymmetric synthesis of S-(+)-2,2-dimethyl Problems with unrecoverable ligands used in the cyclopropanecarboxylic acid method

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