Study On Methods Of Syntheses Two Key Intermediates Of Benazepril

Based on the review of the development of antihypertensive agent and the introduction of ACEI (Angiotensin-Converting Enzyme Inhibitor), the synthesis processes of Benazepril and its key intermediates tert-Butyl (3S)-3-amino-2, 3, 4, 5-tetrahydro-2-oxo-1H-1-benzazepine-1-acetate and Ethyl (R)-2-hydroxy-4-phenylbutanoate have been summarized in the thesis.By analysis of the synthesis processes of tert-Butyl (3S)-3-amino-2, 3, 4, 5- tetrahydro-2-oxo-1H-1-benzazepine-1-acetate, the process with 3 —bromo-2, 3, 4, 5-tetrahydro-2-oxo-1H-benzazepine as a start material was determined. Through a series of reaction, such as halogenated hydrocarbon nucleophilic substitution, N-hydrocarbylation, ethanol amine reduction and (+)-L-tartaric acid resolution, the key intermediate was obtained by overall yield of 54. 9%.Ethyl (S)-2-hydroxy-4-phenylbutanoate and (R, S)-2-hydroxy-4-phenyl butyric acid were synthesized with L-malic acid and DL-malic acid as initial materials by a series of reaction, such as dehydration cyclization, Friedel-Crafts reaction, Pd/C-H₂ reduction and sulfuric acid catalytic esterification. By conversion of the optical configuration of Ethyl (S)-2-hydroxy-4-phenylbutanoate and by application of D-(-)-treo-2-amino-1-(4-nitrophenyl)-1, 3-dihyoxypropane to resolution (R, S)-2-hydroxyl-4-phenyl butyric acid, Ethyl (R)-2-hydroxy-4-phenylbutanoate and (R)-2-hydroxy-4-phenyl butyric acid were obtained.