Preparing method of (S)-3-hydroxy tetrahydrofuran

Abstract

The invention provides a preparing method of (S)-3-hydroxy tetrahydrofuran, which comprises the following steps: (1) adding (S)-4-Cl-3-hydroxy ethyl butyrate, potassium carbonate, benzyl chloride and DMF into a tri-opening bottle, stirring, refluxing, reducing pressure, standing, drying after washing, and recrystallizing; (2) adding tetrahydrofuran and sodium borohydride into a tetra-opening bottle; stirring and dropwise adding (S)-4-Cl-3-benzyloxy ethyl butyrate, continuing to stir, performing rotary evaporation condensing, cooling, neutralizing after stirring, extracting, and rectifying after rotary evaporation condensing; (3) adding (S)-4-Cl-3-benzyloxy-1-butanol, water and concentrated hydrochloric acid into a tri-opening bottle, starting stirring, heating, then performing temperature preserving reaction, neutralizing, extracting, and distilling after rotary evaporation condensing; (4) dissolving (S)-3-benzyloxy tetrahydrofuran in tetrahydrofuran, adding palladium carbon, introducing hydrogen, stirring to react, filtering, concentrating under reduced pressure, adding the recrystallized product, filtering after icy bath cooling, and drying to obtain the (S)-3-hydroxy tetrahydrofuran. The intermediate product is easy to separate and the yield is higher.

Description

Technical field: [0001] The invention relates to the field of pharmaceutical intermediates, in particular to a preparation method of (S)-3-hydroxytetrahydrofuran. Background technique: [0002] The nucleotides, amino acids and monosaccharides that constitute the basic substances of life all have chiral characteristics, and the biological macromolecules nucleic acids, proteins and sugars composed of them all have characteristic spatial structures. This characteristic lays the foundation for the formation and evolution of life , but also to determine the important position of chiral substances in pharmaceutical science. At present, chiral drugs have become a major trend in the development of the pharmaceutical industry due to their unique properties, and the synthesis of single optically active drugs has become an important goal and means of chiral drug research. For example, (S)-3-hydroxytetrahydrofuran is an important intermediate for the synthesis of AIDS drug Amprenavir. ...

AI Technical Summary

Problems solved by technology

[0003] At present, there are two main methods for the preparation of (S)-3-hydroxytetrahydrofuran: (1) reduction-intramolecular etherification of malic acid, using L-malic acid as the starting material, the main defect of this method is the need Use expensive lithium aluminum hydride to reduce malic acid diester, the preparation cost is higher, and by-product is more, and productive rate is not very ideal; - Reduction with sodium borohydride system, and then dehydrochlorination and cyclization under acidic conditions to synthesize (S)-3-hydroxytetrahydrofuran. Extraction and separation are more difficult, reducing yield

However, this method also has certain problems: the hydroxyl protection adopts the alkylation method, the difficulty of separating the intermediate product still exists, and the degree of deprotection is not high enough, resulting in a low actual yield