Method for preparing L-menthyl glyoxylate-hydrate through catalysis of heteropoly acid

Abstract

The invention discloses a method for preparing L-menthyl glyoxylate-hydrate through catalysis of heteropoly acid. The method comprises the following steps: by taking cyclohexane as a water-carrying agent, and heating and backflowing and dehydrating L-menthol and glyoxylic acid water solution under the catalysis of heteropoly acid, to obtain a reaction liquid A; separating the reaction liquid A so as to remove heteropoly acid, and separating to obtain an organic layer; directly adding the organic layer into a sodium sulfite water solution and a sodium hydrogen sulfite water solution, and fully reacting to obtain a reaction liquid B; separating the reaction liquid B to obtain a water layer, regulating the pH value of the water layer to be 6.8-7.5 through base, then adding formaldehyde water solution, and hydrolyzing to obtain the L-menthyl glyoxylate-hydrate. The method is convenient to operate, and the catalysis of the heteropoly acid has both advantages of liquid acid catalysis and solid acid catalysis; the organic layer obtained by filtering the reaction liquid A to remove heteropolyacid, and filtering is not required for the regulation of pH value, so that the emission of waste acid and salt in the production process can be reduced.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a method for preparing L-menthol glyoxylate monohydrate by heteropolyacid catalysis. Background technique [0002] L-menthol glyoxylate monohydrate (compound I) is an important pharmaceutical intermediate widely used in the industrial production of chiral drugs lamivudine (compound II) and emtricitabine (compound III) . [0003] [0004] As an important pharmaceutical intermediate, there are many literature reports on L-menthol glyoxylate monohydrate. Blanco et al. used L-menthol and oxalyl chloride to esterify, and prepared by butyltin reduction. During the reaction, a Dangerous and highly toxic raw materials, not suitable for industrial production (BlancoJ.M.et al, Synthesis, 1998, 11:1590-1592); Silver becomes ester, and then reacts with sodium acetate, and reaction process cost is very high, does not possess suitability for industrialized production condition (Whitesell J...

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Problems solved by technology

[0012] In the production technology, concentrated sulfuric acid is used as a catalyst. Although concentrated sulfuric acid has high catalytic activity, the raw materials and products are easily oxidized during the dehydration process, the reaction is complicated, there are many by-products, and subsequent treatment is troublesome; and concentrated sulfuric acid is serious for equipment corrosion, and there are Environmental pollution caused by waste acid discharge

Luo Huajun etc. disclose a kind of use cyclohexane as water-carrying agent, reduce the oxidation of glyoxylic acid and product menthyl ester in the reflux water separation process of L-menthol glyoxylate monohydrate by reducing the pressure. Preparation method, although the product yield has been improved, but still does not solve the problems such as oxidation caused by using concentrated sulfuric acid (Chemical World, the 11th issue in 2004, 593-596)

[0013] Recently, You Jinzong and others have developed a method for preparing L-menthol glyoxylate monohydrate by using cyclohexane as a water-carrying agent through the catalysis of a solid acid catalyst. Using solid acid instead of concentrated sulfuric acid as a catalyst, it is very good It solves the corrosiveness of concentrated sulfuric acid to equipment, but the solubility of solid acid is poor during the reaction process, and the catalyst needs to be recovered and dried before being reused, and the oxidizing property is still strong

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