普利类药物中间体ECPPA的合成新工艺

New process for medicine intermediate ECPPA

以苯和丁二酸酐为原料经酰化、还原、溴化、酯化反应得到α-溴代苯丁酸乙酯,最后与丙胺酸反应得到普利类药物关键中间体ECPPA.避免了现行生产工艺中钯炭催化加氢脱苄工艺,解决了催化加氢工艺中芳环被加氢的副产物产生.重点对各步反应的工艺参数进行了考察,得到了最佳工艺条件,付克酰基化反应收率为90.3%,羰基的联氨还原收率为88.4%,羰基α-氢的溴化反应收率为85.2%,胺的N-烃基化反应收率为42.9%,以丁二酸酐计总收率为27.7%,为合成ECPPA,降低普利类药物的生产成本提供了一种可行的合成方法.

The process of synthesizing ECPPA, the medicine intermediate of some Angiotensin Converting Enzyme Ingibitors（ACEI）, was developed. Ethyl α-bromophenyl-butyrate was synthesized by Friedel-Crafts Acylation, Wolf Kishner Reduction, halogenation and esterification from benzene and succinic anhydride. ECPPA was synthesized by N-alkylation from α- bromophenylbutyrate and alanine. The yields at the four main steps under improved reaction conditions were 90.3%, 88.4%, 85.2%, 42.9%, respectively, and the overall yield was 27. 7% on the basis of succinic anhydride.