Method for synthesizing S-(+)-tetrahydrofuran-3-methanol

Abstract

The invention discloses a method for synthesizing S-(+)-tetrahydrofuran-3-methanol. The method comprises the following steps: reacting D (+)-10-camphorsulfonic acid with thionyl chloride, so as to obtain D-(+)-10-camphor sulfonyl chloride; reacting D-(+)-10-camphor sulfonyl chloride with (+ / -)-tetrahydrofuran-3-methanol, so as to obtain tetrahydrofuran-3-methyl camphor sulphonate; standing tetrahydrofuran-3-methyl camphor sulphonate to crystallize, performing configuration inversion in the crystallization process, so as to obtain tetrahydrofuran-3-methyl camphor sulphonate of single configuration, dissociating the crystal by using a dissociation agent, so as to obtain S-(+)-tetrahydrofuran-3-methanol. By adopting the method, the phenomenon that only 50% of single configuration can be obtained in the chiral resolution process is avoided, the yield is greatly increased, the synthesis route is short, and the operation is simple. The method is mainly applied to synthesis of a midbody, namely, S-(+)-tetrahydrofuran-3-methanol.

Description

technical field [0001] The invention belongs to the field of preparation of pharmaceutical intermediates, in particular to a method for synthesizing S-(+)-tetrahydrofuran-3-methanol. technical background [0002] Tetrahydrofuran-3-methanol compound is the key intermediate for the preparation of the third-generation nicotinic insecticide dinotefuran and medicine penciclovir, and its molecular structure contains 3-substituted chiral tetrahydrofuran units, while the chiral Different enantiomers of compounds usually have different activities, such as (+)-dinotefuran insecticidal activity is much higher than (-)-dinotefuran ([J].pest Managenment Science,2002,58(2):190 -196; [J]. pest Management Science, 2003, 59(10): 1093-1100). If S-(+)-tetrahydrofuran-3-methanol is used as an intermediate, a single-configuration drug can be obtained to improve drug activity. [0003] At present, the methods of synthesizing S-(+)-tetrahydrofuran-3-methanol reported at home and abroad are all l...

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[0003] At present, the methods of synthesizing S-(+)-tetrahydrofuran-3-methanol reported at home and abroad are all laboratory preparation methods: (Journal of the American Chemical Society, 2009, 131(8), 2786-2787) reported using asymmetric synthesis The catalyst expands the ring of propylene oxide-3-ethanol to S-(+)-tetrahydrofuran-3-methanol, which has problems such as high catalyst cost and complicated synthesis steps;

[0004] (US20100076029) reported that tetrahydrofuran-3-formic acid was reacted with amino acid to obtain S-(+)-tetrahydrofuran-3-methanol through high-performance liquid chromatography separation. This resolution method was low in yield and 50% due to the limitation of chiral resolution method itself. % and limited amount of product separated by HPLC

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