3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester

Abstract

The invention belongs to the technical field of medicines, relates to a method of preparing obeticholic acid through adopting 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester as an intermediate, and particularly relates to the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester that is a chemical compound, a method of preparing the compound, and a use of the compound for preparation of the obeticholic acid. The invention also relates to a method of preparing the obeticholic acid. The method of preparing the obeticholic acid includes (1) preparing the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester and (2) preparing the obeticholic acid through adopting the 3,7-di(t-butyldimethylsiloxy)-6-ene-5beta-cholan-24-oic acid methyl ester as the intermediate.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the compound 3,7-bis(tert-butyldimethylsilyloxy)-6-en-5β-cholan-24-acid methyl ester, the method for preparing the compound and the compound Said compound is used for the purposes of preparing obeticholic acid. The present invention also relates to a method for preparing obeticholic acid, the method comprising the following steps: step (1): preparing 3,7-bis(tert-butyldimethylsilyloxy)-6-ene-5β - cholane-24-oic acid methyl ester; and step (2): using 3,7-bis(tert-butyldimethylsilyloxy)-6-en-5β-cholan-24-oic acid methyl ester as Intermediate, preparation of obeticholic acid. Background technique [0002] Farnesoid X receptor (FXR) belongs to the family of ligand-activated transcription factor nuclear receptors, and its natural ligands include primary bile acid chenodeoxycholic acid, secondary bile acid lithocholic acid and deoxycholic acid, etc. FXR is a bile sensor, and its func...

AI Technical Summary

Problems solved by technology

[0027] Both the literature process route 2 and the literature process route 3 use 3α, 7-bis(trimethylsilyloxy)-6-ene-5β-cholane-24-acid methyl ester as a key intermediate, and these two methods exist The following questions: (1) 3α,7-bis(trimethylsilyloxy)-6-en-5β-cholan-24-oic acid methyl ester (compound 7) contains two trimethylsilyl ether groups, The trimethylsilyl ether group is unstable in nature and is sensitive to acid or alkali, making 3α, 7-bis(trimethylsilyloxy)-6-ene-5β-cholane-24-acid methyl ester It may be hydrolyzed into a monosilyl ether product during post-processing, which affects the yield and purity of the final product; (2) in the preparation of 3α, 7-bis(trimethylsilyloxy)-6-ene-5β-cholesterol In the process of alkane-24-acid methyl ester, need to use LDA (tetrahydrofuran solution), this reagent is expensive, and must be sealed and preserved under anhydrous condition, has increased the difficulty of storage and transportation, and needs to use in anhydrous condition Down operation, not easy to use

Images