盐酸贝那普利的合成

Synthesis of Benazepril Hydrochloride

以L-苹果酸为手性源,经成酐活化、傅-克反应、常压氢化和酯化反应制得(S)-2-羟基-4-苯基丁酸乙酯(8),8经甲磺酰化活化后经与丙酸钾反应和水解制得构型反转的(R)-2-羟基-4-苯基丁酸乙酯(3)。3经磺酰化活化后与(3S)-3-氨基-2,3,4,5-四氢-2-氧代-1H-1-苯并氮-1-乙酸叔丁酯(2)反应后水解、成盐制得盐酸贝那普利,总收率约32%。

L-malic acid underwent activation, Friedel-Crafts reaction, reduction and esterification to get ethyl （S）-2-hydroxy-4-phenylbutyrate, then followed by methylsulfonation, substitution and hydrolysis to give ethyl （R）-2- hydroxy-4-phenylbutyrate （3）. Benazepril hydrochloride was synthesized by condensation of 3 and actived tert-butyl （3S）-3-amino-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate （2） followed by hydrolysis and salification with an overall yield of about 32 % （based on L-malic acid）.