Method for preparing tetrahydropyrane-3-boronic acid pinacol ester

Abstract

The invention discloses a novel method for preparing tetrahydropyrane-3-boronic acid pinacol ester. The new method specifically comprises the following steps: taking a dextrorotation alpha pinene and dimethyl sulfide borane complex compound as raw materials, preparing di-alpha pinene borane, then reacting with 3,4-dihydropyran at a room temperature, reducing with anhydrous acetaldehyde to generate dimethyl borate, needing no intermediate separation and successively reacting with pinacol to generate a target product, namely the tetrahydropyrane-3-boronic acid pinacol ester. The method has the obvious advantages of high easiness in obtaining of reaction raw materials, high simplicity in reaction operation, high easiness in realization of mass production, high yield, good purity and low production cost.

Description

technical field [0001] The invention relates to a new method for synthesizing a pharmaceutical intermediate organic borate, belonging to the field of organic chemical synthesis, in particular to a method for preparing tetrahydropyran-3-boronic acid pinacol ester. Background technique [0002] Organoboronic acid and its derivatives are an important class of pharmaceutical intermediates and organic chemical reagents, which are widely used in organic synthesis to form new C-C single bonds through Suzuki-Miyaura coupling reactions. Most organic boronic acids are stable at room temperature and can be stored for a long time, but some alkyl boronic acids and alkene or alkyne boronic acids are unstable at room temperature and are prone to deterioration, so it is difficult to preserve this type of boronic acid. Certain difficulties, if this type of boric acid is converted into boric acid derivatives such as boric acid esters, its properties are stable and can be stored for a period o...

AI Technical Summary

Problems solved by technology

The raw material 3-bromotetrahydropyran of this method is very expensive, and its market price is roughly 5500RMB / 100g, and the initial initiation of this reaction is a strong exothermic process, and the temperature can rise to More than 100 degrees, and then the temperature will slowly drop to room temperature, so it is difficult to control the reaction process, which will affect the reaction yield. The yield of this preparation method is only 27%, and the target product in milligrams can only be prepared in the laboratory. Scale-up synthesis, so this method cannot realize industrial production

[0009] The above two known preparation methods all have the disadvantages of expensive raw materials, difficult to obtain, harsh reaction conditions, low utilization rate of raw materials, and inability to realize scale-up production, all of which limit the mass production of the target product

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