Synthesis method of cycloalkene-1-boronic acid pinacol ester

Abstract

The invention discloses a synthesis method of cycloalkene-1-boronic acid pinacol ester. The synthesis method comprises three reaction steps of enabling cycloketone to react with phosphorus pentachloride to obtain 1-cycloolefin chloride, preparing cycloalkene-1-boronic acid through 1-cycloolefin chloride, lithium metal and a boronizing agent by the one-step method, and enabling cycloalkene-1-boronic acid to react with pinacol to obtain the final product. According to the method, the reaction is under mild conditions, 1-cycloolefin chloride can directly enter the next reaction without distilling and purifying, and intermediates and products obtained in each step do not need distilling, so that the operation is simple, and moreover, the raw materials are low in cost and easy to obtain, and as a result, mass production can be performed.

Description

technical field [0001] The invention relates to a synthesis method of cycloalkenyl-1-boronic acid pinacol ester, which belongs to the field of organic chemical synthesis. Background technique [0002] In modern drug synthesis, it is more and more common to introduce cycloalkenyl as a common structural unit, and it is often introduced as a substituent group to investigate the structure-activity relationship. In recent years, cycloalkenylboronic acid pinacol ester and corresponding It is more common for aromatic or heterocyclic halides to introduce cycloalkenyl groups through suzuki coupling reactions (references Billingsley, Kelcin; Barder Timthye. Angewandtechemle.International Edition; vol.46;nb:28;(2007);p 5359-5363) , its synthesis method has the following several kinds: [0003] Method 1: Reported in J.AM.CHEM.SOC.VOL.130.NO.2008.8481-8490 [0004] . [0005] However, this method has many defects: (1) The reaction requires ultra-low temperature, and the industrial ...

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Problems solved by technology

[0005] However, this method has many defects: (1) The reaction requires ultra-low temperature, the industrial scale-up operation is cumbersome, and the refrigeration cost is increased; (2) The selectivity of the reaction is very poor, and there are many impurities , the yield is low and the purification is difficult during vacuum distillation; (3) 4eq butyllithium is used in the literature, and isopropoxy borate pinacol ester needs to be self-made, the cost of raw materials is high and there are safety hazards in operation; (4) The p-toluenesulfonyl hydrazide used in the literature forms an oxime with a ketone and then leaves, and its molecular weight is very large, and the atom utilization rate is low

[0008] The disadvantage of this method is: (1) Although 1-chlorocyclohexene (intermediate 1) is also prepared by itself, the purity requirement is too high, and its purity It directly affects the purity of the product, so the raw material needs to be rectified, and the product also needs to be obtained by rectification, and the operation is cumbersome; (2) This reaction uses a precious metal palladium catalyst, and the raw material is expensive

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