Synthetic method of thiophene-3-ethanol

Abstract

The invention discloses a synthetic method of thiophene-3-ethanol. The method comprises the following steps of: adding a halogenated hydrocarbon solvent and ethylene glycol into a reaction kettle, dropwise adding thionyl chloride and preserving heat for reacting; separating liquid and extracting to obtain an organic phase containing a substance shown in the specifications; adding a ruthenium trichloride aqueous solution and a sodium bicarbonate aqueous solution in the presence of the halogenated hydrocarbon solvent and dropwise adding a sodium hypochlorite aqueous solution; after detecting that a system does not have oxidizing property, performing liquid separation, concentration, devitrification and drying to obtain a substance shown in the specifications, adding an ester solvent and butyl lithium into a reaction kettle, adding a prepared ester solution of tribromothiofuran and a prepared ester solution of the substance, separating the liquid and extracting to obtain a system containing a substance shown in the specifications; and adding a dilute sulfuric acid into the system containing the substance shown in the specifications, concentrating, neutralizing, extracting and concentrating to obtain an end product. The method has the advantages of high reaction purity and yield, stable process condition, easiness for operation and mass production capability; and the thiophene-3-ethanol is prepared from tribromothiofuran by performing low-temperature lithiation, so that the use of epoxy ethane serving as an explosive hazard is avoided, and mass production becomes possible.

Description

(1) Technical field: [0001] The invention relates to a method for synthesizing thiophene-3-ethanol. (two) background technology: [0002] Thiophene-3-ethanol is used as an intermediate of antithrombotic drug ticlopidine. It has a good effect and prospect in thienopyridine drugs, especially ticlopidine hydrochloride and clopidogrel. Therefore, a high-efficiency, low-cost thiophene-3-ethanol synthesis process is of great significance. [0003] At present, the methods for preparing thiophene-3-ethanol mainly contain the following: [0004] (1) Both the Grignard reagent method and the sodium reagent method use thiophene as a raw material to obtain the metal compound of thiophene through different steps, then react with ethylene oxide, and then hydrolyze to obtain thiophene-3-ethanol. These two methods The material used contains ethylene oxide, which is an explosive and dangerous product, and it is more dangerous in the production process; [0005] (2) The ester reduction met...

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Problems solved by technology

[0004] (1) Both the Grignard reagent method and the sodium reagent method use thiophene as a raw material to obtain the metal compound of thiophene through different steps, then react with ethylene oxide, and then hydrolyze to obtain thiophene-3-ethanol. These two methods The material used contains ethylene oxide, which is an explosive and dangerous product, and it is more dangerous in the production process;

[0005] (2) The ester reduction method is to use thiophene acetate as a raw material, and under the action of a catalyst, the ester is reduced to a primary alcohol; the yield of this method is relatively low;

[0006] (3) Using methanol and thiophene-3-acetic acid as starting materials, react in a hydrogen chloride system to first obtain thiophene-3-ethanol methyl ester, then thiophene-3-ethanol methyl ester is then used in tetrahydrofuran system with lithium aluminum hydride Carry out reduction to obtain thiophene-3-ethanol; but the raw material thiophene-3-acetic acid price of this method is higher, is not suitable for large-scale production;

[0007] (4) Using tribromothiophene as the starting material, after adding butyllithium dropwise, add 1,3,2-dioxazolethiophene-2,2-dioxide At present, the methods reported in the literature are to add butyllithium dropwise to the tribromothiophene system. The final product obtained by this method contains isomer impurities that are difficult to remove, and the yield is low

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