Synthesis Of The Ace Inhibitor Benazepril Intermediates

Benazepril( I )is an angiotension converting enzyme(ACE) inhibitor which was in market as early as 1990.It is therapeutic agents for the treatment of hypertension. The side effection is very limited. According to the latest reporting,such ACE inhibitors also have potential treatment of some other diseases. Major two intermediates for synthesizing of benazepril are a -oxo-phenylbutyric acid( III ) and (3 s)-3 -amino-2,3 ,4, 5-tetrahydro-2-oxo- I H-I -benza.zeprin- 1-acetic acid-(tert-butyl) ester( II ).The main purpose of this paper is to study on synthesis of these two organic intermediates. Compound II is synthesized through eight steps using 1-Tetralone as starting materiai. Racemis compound II is resolved with L-tartaric acid in the presence of benzaldehyde to get rotating isomer II . During the process of preparing II , 1-Tetralone,Potassium phthalimide,and tert-butyl Bromoacetate are also prepared as starting materials. Under these optimum, the yield of intermediates is equal or higher than literature, the technological process is simplified and the cost is reduced. These all will benefit to industrializing. The major intermediates?structure is certified by IR,-N7MR and MS. The other intermediate a -oxo-phenylbutyric acid(II1) is also prepared. Three different methods are tested. The best method is to use Benzenepropanoic acid ethyl ester as starting material with high and stable yield as high as 89%. The operation conditions are optimized by optimum seeking methods The structure is characterized by -NMR. The successful preparation of II and III make the foundation on synthesizing Benzzepril.