A kind of synthetic method of promestriene

Abstract

The invention relates to a method for synthesizing the compound promestrine, which is a derivative of estradiol, has estrogen characteristics, and plays an important role in regulating and promoting the normal development of female sexual organs and side features. The present invention adopts estradiol as a starting material, and prepares 3-propoxyl-17β-hydroxyestradiol-1,3,5(10)-triene by reacting it with n-bromopropane in an acetone solvent under the catalysis of sodium hydroxide base , and then use sodium hydride as a basic catalyst in tetrahydrofuran solvent, and methyl iodide as a methylating reagent to prepare promestriene. The synthesis method has the advantages of mild reaction conditions, low solvent or reagent toxicity, convenient post-treatment, high yield, low synthesis cost, and environmental friendliness.

Description

technical field [0001] The invention relates to a synthesis method of promestrine, which belongs to the field of organic chemical synthesis. Background technique [0002] Promestriene, also known as Promestriene, its English name is Promestriene, its chemical name is 3-propoxy-17β-methoxyestro-1,3,5(10)-triene, and its structural formula is as follows: [0003] [0004] Proestrene has estrogenic properties and plays an important role in regulating and promoting the normal development of female sexual organs and side features. Compared with other estrogens, the drug is absorbed into the systemic circulation in a small amount after use, and the systemic hormone effect is mild. It is clinically used as a local estrogen supplement, and is suitable for estrogen-deficiency vaginal atrophy and postpartum, surgery or physical therapy. Delayed cervicovaginal and vulvar healing. It was first developed by Dalimei Pharmaceutical Factory in Monaco, and it applied for the British pat...

AI Technical Summary

Problems solved by technology

[0007] Patent GB1337198A reports that when the intermediate 3-propoxyl-17β-hydroxyestr-1,3,5(10)-triene is synthesized in the first step, the base used is sodium ethoxide prepared by reacting sodium metal with absolute ethanol , the reaction has the disadvantages of metal sodium being difficult to control, harsh process conditions, high risk, and high cost; the second step of promestriene is to use sodium hydride and dimethyl sulfoxide to prepare sodium dimethyl sulfoxide solution, 3 -Propoxy-17β-hydroxyestr-1,3,5(10)-triene was treated with sodium dimethyl sulfoxide solution and etherified with dimethyl sulfate to obtain promestrine, but dimethyl sulfoxide It is a strong polar aprotic solvent with a high boiling point and is easily soluble in water. It is expensive and difficult to recycle. It is not only difficult to recycle, but also affects the product yield.

In 2008, Cui Jiantong and others improved the synthesis method of the first step reaction of the original research method, 3-propoxy-17β-hydroxyestr-1,3,5(10)-triene, and adopted the phase transfer catalysis method. Inexpensive sodium hydroxide replaces sodium ethoxide, but a phase transfer catalyst, n-tetrabutylammonium bisulfate, is used to complicate the process

In 2014, Yang Jing and others replaced dimethyl sulfate with less toxic methyl iodide in the second step reaction of the original research method, but continued to use the high boiling point solvent dimethyl sulfoxide, which was expensive and difficult to post-process

Images