Notiz zur Synthese Eines Optisch Aktiven Ace‐Hemmers mit Amino‐oxo‐benzazepin‐1‐alkansäure‐Struktur mittels enantiokonvergierender kristallisationsinduzierter Racemat‐Trennung

Abstract

An enantioselective synthesis of the potent angiotensin-converting enzyme inhibitor (I'S,3S)-3-[( 1'-(ethoxycarbonyl)-3'-phenylpropyl)amino]-2,3,4,5-tetrahydro-2-0~0-1~~ I-benzazepine-I-acetic acid hydrochloride (3) is described which uses a crystallization-based resolution of a racemic amino intermediate with concomitant racemization ofthe unwanted enantiomer.

Isolation and characterization of benazepril unknown impurity by chromatographic and spectroscopic methods

“…The substantial difference was observed for C 17 resonance, which was shifted towards lower energy side by about 41 ppm indicating the presence of electron withdrawing -OH group. Moreover, the adjacent carbons (C 18 and C 13 ) also exhibited similar behavior while a minor change was noted for C 4 as a result of its interaction with C 17 thus corroborating the influence of the hydroxyl group [11,12]. The DEPT 135 carbon analysis indicated the presence of five CH 2 groups instead of six, thus confirming the presence of an OH group on one of the CH 2 group.…”

Formal Synthesis of the ACE Inhibitor Benazepril·HCl via an Asymmetric Aza-Michael Reaction

“…First, we used commercially 40% aqueous glyoxylic acid and o-nitroacetophenone (5) as starting materials to prepare 4-(2-nitrophenyl)-4-oxo-but-2-enoic acid methyl ester (6) via an aldol condensation reaction [8] (Scheme 2). A large coupling constant (15.6 Hz) for the olefinic protons, which appeared at δ 7.3 and 6.4, suggested a trans geometry for the double bond.…”

“…Compound 4 has been a quite popular subject over the years in both academic and industrial sectors, but only a few papers have been published concerning its synthesis. Both Watthey [4] and Boyer [5] used α-tetralone as starting material to prepare benazepril•HCl (4), and both their synthesis went through rather tedious resolution processes. Herein, we describe a convergent pathway in which compound 8, a key chiral intermediate to benazepril•HCl (4), was prepared through an asymmetric aza-Michael reaction.…”

Asymmetric Synthesis of N-Substituted α-Aminobenzlactam via Crystallization-Induced Asymmetric Transformation of Covalent Diastereomer

“…Unsubstituted aminobenzlactam 3 is also an important precursor for a growth hormone secretagogue, L-692,429 . Asymmetric synthesis of 1 and subsequent transformation of it into 2 were demonstrated by Wetter . Approaches to the asymmetric synthesis of 3 have been reported by a Merck group .…”