| 摘要 |
<p>Industrial preparation of (2S, 3aS, 7aS)-prehydroindole-2-carboxylic acid (I) and its esters. <??>Industrial preparation of (2S, 3aS, 7aS)-prehydroindole-2-carboxylic acid (I) and its esters comprises: <??>(1) reacting 2,7-oxepanedione (III) with a protected halogenated amino acid (IV) in the presence of zinc or a zinc/copper amalgam; <??>(2) removing the amino protecting group to give (V); <??>(3) cyclizing (V) with a chlorinating agent or a peptidic coupler to give (VI); <??>(4) coupling (VI) in the presence of titanium to give (VII); and <??>(5) performing catalytic hydrogenation of (VII) in the presence of palladium, rhodium, or nickel. <??>R = H, benzyl, or 1-6C alkyl; <??>R1 = benzyl, or 1-6C alkyl; <??>R2 = a protecting group that is different from R1; <??>X = Br or I. <??>Independent claims are also included for: <??>(1) compounds of formula (VI); and <??>(2) the synthesis of perindopril and its salts using (I) prepared as above.</p> |
