爱普列特的合成工艺改进

Improved Synthesis of Epristeride

本文对爱普列特(1)的合成方法进行改进。以3-羰基雄甾-4-烯-17β-羧酸甲酯(2)为原料,经水解、胺化得缩合物N-叔丁基-3-羰基雄甾-3,5-二烯-17β-甲酰胺(4),4在DTBMP催化下与三氟甲磺酸酐反应得N-叔丁基-3-三氟甲磺酰基雄甾-3,5-二烯-17β-甲酰胺(8)。8在PdCl2(PPh3)2和三乙胺存在下,通入一氧化碳反应得17β-(N-叔丁基氨甲酰基)雄甾-3,5-二烯-3-羧酸甲酯(9),最后经水解得到1。该法无需使用1,1,2,2-四氟-2-(1,1,2,2-四氟乙氧基)乙烷磺酰氟(10),反应条件温和、操作简便,1次精制纯度99.93%,反应总收率50.9%(以2计)。

The synthetic method of epristeride(1)was improved.Methyl 3-oxoandrosta-4-ene-17β-carboxylate(2)is hydrolyzed and aminated to give N-tert-butyl-3-oxoandrosta-3,5-diene-17β-formamide(4).Then 4 reacted with Tf2O catalyzed by DTBMP to afford N-tert-butyl-3-trifluoromethylsulfonylandrosta-3,5-diene-17β-formamide(8).In the presence of PdCl2(PPh3)2 and Et3N,intermediate 8 reacted with carbon monoxide to obtain 17β-(N-t-butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid methyl ester(9).Finally,the target compound was obtained by hydrolysis of 9.This method,without 1,1,2,2-tetrafluoro-2-(1,1,2,2-tetrafluoroethoxy)ethanesulfonyl fluoride,has mild reaction conditions and simple operation with a purity of 99.93%,and the total yield was 50.9%(based on 2).