Method for preparing idebenone

Abstract

The invention relates to a preparation method for idebenone, comprising the following steps: (1), 3,4,5-trimethoxy-toluene has friedel-crafts reaction with 10-acetoxy-decane chloride or 10-acetoxy-decanoyl- bromine to generate 6-(10-acetoxy-1-oxo-decane yl)-2,3-dimethoxy-5-methyl phenol; (2), the 6-(10-acetoxy-1-oxo-decane yl)-2,3-dimethoxy-5-methyl phenol obtained in the step (1) is reacted with hydrogen under the joint effect of palladium-carbon catalyst and dehydrating agent DCC to generate 6-(10-acetoxy-decyl)-2,3-dimethoxy-5-methyl phenol; (3), the6-(10-acetoxy-decyl)-2,3-dimethoxy-5-methyl phenol prepares 6-(10-hydroxy decyl) -2,3-dimethoxy-5-methyl phenol through hydrolysis; (4), the 6-(10-hydroxy decyl) -2,3-dimethoxy-5-methyl phenol has oxidation reaction with an oxygen-supply body under the effect of catalytic oxidizer Cu (Salen) so as to generate the idebenone. The preparation method has low cost and high yield, which is suitable for large-scale industrial idebenone production.

Description

technical field [0001] The invention belongs to the field of organic medicine synthesis, in particular to a preparation method of idebenone. Background technique [0002] Idebenone (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methylbenzoquinone) is a drug for improving brain function developed by Takeda Corporation in Japan, which is clinically used for the treatment of cerebral infarction, cerebral Hemorrhage, brain dysfunction caused by cerebral arteriosclerosis sequelae, low consciousness, emotional disturbance, language disorder and dementia, etc., as a central nervous system drug, idebenone has received widespread attention from the medical industry. [0003] At present, the synthetic method of idebenone reported in the literature mainly consists of the following three kinds: [0004] (1), 3,4,5-trimethoxytoluene introduces 10-acetoxydecanoyl through Friedel-Crafts reaction, then successively undergoes hydrolysis, reduction, and oxidation to obtain idebenone, with a yield of a...

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Problems solved by technology

[0010] Combining the above three methods, method (1) although the steps of the method are convenient to operate and the yield is high, but its steps are the longest, and the oxidant Friedman's salt used for the oxidation of intermediate 5 has a great potential safety hazard during preparation , and can cause environmental pollution; compared with method (1), method (2) is first oxidized to quinone, then reduces the side chain, and the last step adopts lithium aluminum hydride as a reducing agent, which has high cost and certain danger , the biggest disadvantage is that the process yield is low, and industrial production cannot be realized; the method (3) has the shortest step, but the reaction raw material of this method contains peroxide, which has great danger and is not suitable for large-scale production

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