群多普利中间体(2β,3aβ,7aα)-八氢吲哚-2-羧酸的合成

Synthesis of(2β,3aβ,7aα)-octahydroindole-2-carboxylic acid intermediate of Trandolapril

以1,1,3,3-四甲氧基丙烷为原料,经选择性水解、硝基甲烷缩合、脱水、Diels-Adler加成、加压氢化、水解并环合、腈基水解7步反应,得到用于合成心血管药物群多普利的关键中间体(2β,3aβ,7aα)-八氢吲哚-2-羧酸。产物及中间体经1HNMR及MS确证。此反应路线工艺相对简单,成本较低,经优化后,总收率为10.1%。

The synthesis of （2β,3aβ,7aα）-octahydroindole-2- earboxylie acid, which is used as the key intermediate for synthesis of Trandolapril-a cardiovascular drug, was described in this paper. （2β,3aβ,7aα ）-Octahydroindole-2-carboxylic acid was synthesized from 1,1,3,3-tetramethoxy propane through selective hydrolysis, condensation with nitromethane, dehydration, the Diels-Adler addition, hydrogenation under pressure, hydrolysis and cyclization, and hydrolysis of nitrile. By optimizing the preparation operations, the total yield of product obtained after these seven steps was 10.1% .The product was characterized by means of ^1HNMR and MS.The results indicated that this route was feasible, featuring a relatively simple process and a good potential for scale-up.