Hydroxy removing process for eplerenone intermediate

Abstract

The invention discloses a hydroxy removing process for an eplerenone intermediate 5beta-cyan-11alpha,17beta-dihydroxy-3,5'-oxo-4,7-methylene-21-carboxylic acid-17alpha pregna-gamma-lactone compound in a formula I. The process comprises the following steps of: reacting an eplerenone intermediate and an acid hydroxy removing agent in a solvent at a certain temperature, separating out ice water after the reaction is finished, adjusting the solution to be neutral by using alkali solution, filtering the solution, and drying the filtrate to obtain an eplerenone intermediate hydroxy removed 5beta-cyan-9(11)-alkene-17beta-hydroxy-3,5'-oxo-4,7-methylene-21-carboxylic acid-17alpha pregna-gamma-lactone compound in a formula II.

Description

technical field The present invention relates to a dehydroxylation process of an eplerenone intermediate, in particular to an eplerenone intermediate 5β-cyano-11α,17β-dihydroxy-3,5'-oxo-4,7 -Dehydroxylation process of methylene-21-carboxylic acid-17α-pregna-γ-lactone. Background technique Eplerenone (compound of formula Ⅲ) is a new type of selective aldosterone receptor blocker. It has minimal interaction with androgen and progesterone receptors, and has a long half-life. It can effectively control high blood pressure by taking it orally once a day. Blood pressure, reduce damage to heart, brain and kidney and other target organs, improve microalbuminuria in patients with type 2 diabetes, and its side effect rate is similar to that of placebo, and it is well tolerated. Eplerenone is of great significance in controlling hypertension in hypertensive patients, preventing cardiovascular diseases related to target organ damage, and improving the prognosis of hypertensive patients...

AI Technical Summary

Problems solved by technology

Among them, the sulfonation reaction is the most critical step in determining the quality and yield of the final product. The HPLC of the method provided in WO 98 / 25948 has only 76% of the dehydroxylated product, and it is difficult to separate in an oily state, where Δ 11（12） Reaching 10% to 16%, it can only be separated and purified by column chromatography, which brings great obstacles to large-scale production

Although another route provided in WO 98 / 25948 avoids the difficulty of separation and purification caused by the elimination of 11a-hydroxyl, we found through our research that when 11a-hydroxyl does not exist, the yield of cyanation reaction will be greatly affected