New technology for synthesizing Corey lactonic acid by one-pan boiling method

Abstract

A process for one-pot synthesis of Corey lactone, characterized in that it comprises selecting 2-halo-5-oxobicyclo[2.2.1]heptane-7-carboxylic acid and ester derivatives having the formula I as raw material, adding oxidant, alkalizing with base, acidifying with acid, completing the oxidation of material, ring-opening, cyclization continuously in the same reactor, and purifying to obtain the production 5-hydroxy-hexahydro-2-oxo-2H-cyclopenta[b]furan-4-carboxylic acid having the formula II, i.e. Corey lactone. In the process for one-pot synthesis of Corey lactone having the formula II, Corey lactone is easy to be resolved and is the key intermediate for synthesis of prostaglandins. The method is simple to operate and the raw materials are cheap and easy to be obtained. The method has low pollution to environment and can reduce the cost for producing Corey lactone with large range.

Description

technical field [0001] This patent relates to the synthesis method of the key intermediate Corey lactone in the total synthesis of prostaglandin compounds. Background technique [0002] Prostaglandins (PGs) are an important class of endogenous physiologically active natural products with extremely low content in biological tissues. They were discovered by von Enler in 1930, and their skeleton is a five-membered ring Carboxylic acid with 20 carbon atoms, according to the structural difference of the five-membered ring, the natural prostate can be of types such as PGA, PGB, PGC, PGE and PGF. has an effect. [0003] Through the study of natural prostaglandins and their structural modification, a large number of prostaglandin drugs have emerged, which are widely used, such as the drug dinoprostone (PGE) used to induce labor. 2 ), alprostadil (PGE 1 ), drugs for glaucoma treatment Travoprost (Travoprost) and Latanoprost (Latanoprost) and so on. [0004] figure 1 [0005] It...

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Problems solved by technology

[0013] 1. Using the step-by-step synthesis method, the 3-step reaction needs to use 2 or even 3 reaction vessels to complete the synthesis of Corey lactone acid, and the separation and purification of each step is cumbersome;

[0014] 2. The domestic quality of m-chloroperoxybenzoic acid used in the oxidation reaction is average, while the imported price is relatively expensive, and high-concentration peracetic acid is difficult to purchase;

[0015] 3. M-chloroperoxybenzoic acid and peracetic acid are easy to release oxygen, which is unsafe for storage and transportation. The higher the purity, the greater the danger, especially the high concentration of peracetic acid, which is extremely explosive;

[0016] 4. It is difficult to separate m-chlorobenzoic acid and the target product after the reaction of m-chloroperoxybenzoic acid. The separation effect of silica gel column chromatography is good, but a large amount of elution solvent is required, and the cost is high, which limits industrialized large-scale production;

[0017] 5. Using m-chloroperoxybenzoic acid or peracetic acid as an oxidizing agent, the yield is not very high

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