A kind of chemical synthesis method of 8-furan-8-oxooctanoic acid methyl ester

Abstract

The invention relates to a chemical synthetic method of 8-furan-8-oxomethyl caprylate. The method comprises the following steps of adding octanedioic acid and sulfoxide chloride into a reaction bulb, agitating an obtained mixture at a room temperature until a reaction is complete, and distilling to remove the sulfoxide chloride under normal pressure; afterwards, adding a solvent and a catalyst into the reaction bulb to carry out another reaction, dropwise adding methanol into the reaction bulb for quenching, decompressing the reaction bulb and distilling to remove the solvent, dissolving a target product by using an extracting solution to obtain a solution, and distilling the solution under reduced pressure to obtain a yellowish oily 8-furan-8-oxomethyl caprylate pure product. According to the chemical synthetic method of the 8-furan-8-oxomethyl caprylate, a synthetic strategy of a one-pot method is adopted; by proceeding from the low-cost octanedioic acid, the octanedioyl chloride is prepared with a high yield; afterwards, the octanedioyl chloride and furan are subjected to a regioselectivity Friedel-Crafts acylation reaction; finally, acyl chloride at the other end is quenched by using the methanol to directly generate methyl ester to obtain the product; by using the method, the synthetic route of the target product is simplified; the reaction time is greatly shortened; the synthetic total yield is improved; therefore, the production cost is decreased; the chemical synthetic method has the advantages of being low in cost, higher in yield, simple to operate and suitable for industrial production, and the like.

Description

technical field [0001] The invention relates to a method for synthesizing methyl 8-furan-8-oxooctanoate, a key intermediate of misoprostol and alprostadil, using suberic acid as a starting material. Background technique [0002] Misoprostol is a prostaglandin E 1 It is usually used orally for the prevention and treatment of gastric and duodenal ulcers caused by non-steroidal anti-inflammatory drugs (NSAIDs). Ulcer prophylaxis. At the same time, the drug can also be used in combination with mifepristone to terminate early pregnancy within 49 days of menopause, and is rated as a 1A drug with the highest priority by the FDA. [0003] The bulk drug is obtained from the intermediate 8-furan-8-oxooctanoic acid methyl ester through reduction and rearrangement, and then Michael addition with alkenyl Grignard reagent. As a key intermediate of misoprostol, the chemical synthesis methods of methyl 8-furan-8-oxooctanoate mainly contain the following types: [0004] 1) Use suberic ac...

AI Technical Summary

Problems solved by technology

Due to the high price of methyl 8-iodooctanoate, the anhydrous and oxygen-free operation is cumbersome, the reaction conditions are harsh, and the use of cuprous cyanide in the reaction process is highly toxic, which limits its industrial application. The synthetic route is as shown in equation (2) :

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