Preparation method of optically pure 2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid

Abstract

The invention provides a preparation method of optically pure 2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid, and relates to the technical field of Corey lactone intermediate synthesis. The preparation method comprises the following steps: (1) preparing racemate 2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid from norbornadiene HR through two steps: Prinee reaction and Jones oxidation; (2) mixing the product with isopropyl acetate to obtain white crystals namely optically pure (+)-2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid (S)-(-)-N-benzylbenzene-alpha-phenylethylamine salt; and (3) extracting the product obtained in the step (2) by ethyl acetate to obtain the final product namely optically pure 2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid. The method is simple and convenient,is easy to operate, and is beneficial for the industrial production.

Description

technical field [0001] The invention relates to the technical field of synthesis of corey lactone intermediates, in particular to a preparation method of optically pure 2-oxotricyclo[2.2.1.0]-heptane-7-carboxylic acid. Background technique [0002] Prostaglandins (PGs) are an important class of endogenous physiologically active natural products, which have effects on the reproductive system, nervous system, respiratory system, and endocrine system. Through the research and structural modification of natural prostaglandins, a large number of prostaglandin drugs with a wide range of uses have been synthesized, among which FP receptor agonists for the treatment of glaucoma are one of the research hotspots in recent years. There are many chiral centers of prostaglandin drugs, and the synthetic route is lengthy. A number of synthetic routes have been developed, among which the route developed by the Corey group can be regarded as one of the milestones in the history of organic s...

AI Technical Summary

Problems solved by technology

Subsequent literature shows that the method has poor reproducibility and low yield, and most of the resolved solvents are mixed solvents, which is not conducive to industrial production and recycling

Due to the deficiency of the diastereomer crystallization method, the research on the bioresolution method has been going on for decades, and several methods have been developed. At present, the enzymatic efficiency of the bioresolution method is still not satisfactory, and The corresponding reaction system has relatively high requirements on pH, temperature and other conditions, the reaction volume is relatively large, and the source of some enzymes used is less, which is not suitable for large-scale production. 1.0] The method of heptane-7-carboxylic acid is necessary