Joint production method for (S)-3-hydroxyl-gamma-butyrolactone, (S)-3-hydroxyl tetrahydrofuran

Abstract

The present invention discloses a joint production method of (S)-3-hydroxyl-Gamma-butyrolactone and (S)-3-hydroxyl tetrahydrofuran. The production method comprises the following steps: firstly, L-malic acid is added into methanol, inorganic acid is added for catalysis, the solid is dissolved and reflows, and then is decompressed and dried through evaporation, the methanol and thionyl chloride are added, the reaction solution is heated and reflows, and the L-malic acid can be produced; secondly, the L-malic acid and tetrahydrofuran are mixed, a reducing agent and a catalyst are added for catalysis, and the (S)-1, 2, 4-trihydroxybutane aqueous solution and (S)-3, 4-hydroxy sodium butyrate are respectively produced; thirdly, water is vaporized from the (S)-1, 2, 4-trihydroxybutane aqueous solution, and the (S)-3-hydroxyl tetrahydrofuran is synthesized through catalytic ring closure, the pH of the (S)-3, 4-hydroxy sodium butyrate aqueous solution is adjusted, the (S)-3, 4-hydroxy sodium butyrate aqueous solution reflows, is dried through evaporation and extracted with ethyl acetate, and the (S)-3-hydroxyl-Gamma-butyrolactone can be produced. The present invention has the advantages that raw materials are cheap, the dosage of the thionyl chloride is reduced, and the production method has less environmental pollution.

Description

technical field [0001] The invention belongs to the field of organic chemistry, in particular to a joint production method of optically pure (S)-3-hydroxyl-γ-butyrolactone and (S)-3-hydroxytetrahydrofuran. Background technique [0002] (S)-3-Hydroxy-γ-butyrolactone is an important organic synthesis intermediate and chiral source compound, which is a key intermediate in the synthesis of neuromodulator (R)-γ-amino-β-hydroxybutyric acid It is also a key intermediate for the preparation of blood lipid-lowering drug atorvastatin, nerve mediator L-carnitine, HIV protease inhibitor amprenavir, and anticancer drug aplysistain. The (S)-3-hydroxyl-4 -Bromobutyric acid is a potential stabilizer. [0003] The synthetic method of (S)-3-hydroxyl-γ-butyrolactone mainly contains: [0004] 1. Using malic acid as raw material, [Chem.Lett., 1389-1392 (1984)] converts malic acid into dimethyl or diethyl malate, reduces it with a metal boron compound, and then synthesizes (S) through acid cata...

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Problems solved by technology

[0006] 2. Using maltose [US6,713,290A] as a raw material to synthesize (S)-3-hydroxy-γ-butyrolactone after oxidation and acid catalysis, but the composition of the reaction mixture in this method is quite complicated, and it needs to be separated from the complex components It is difficult to extract the desired lactone, resulting in low lactone content

Due to the limitation of raw materials, the optical purity of this route is not high and the product purification is relatively difficult.

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