Patent ID: 6133308
Filing Date: 2000-10-17
Classification: A61P,C07B,C07C,C07D

Abstract:
A process for forming a .gamma.-lactam carboxylic acid of Formula V: ##STR42## or a salt thereof, wherein R.sup.1 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkaryl, aralkyl, where the ring portion of any of said aryl, aralkyl, or alkaryl can be optionally substituted;R.sup.2 is alkyl, cycloalkyl, aryl, alkaryl, aralkyl, alkoxy, hydroxy, alkoxyalkyl, or amido, where the ring portion of any of said aryl, aralkyl, or alkaryl can be optionally substituted; andsaid process comprising:(a) deprotonating a substituted aryl or heteroaryl oxazoline of Formula I: ##STR43## where R.sup.1 is as defined above; R.sup.3 is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkaryl, any of which can be optionally substituted; andR.sup.4 is aryl or heteroaryl, either of which may be optionally substituted;by treating said substituted aryl or heteroaryl oxazoline with a strong base to form an enolate;(b) transmetallating said enolate with a metal selected from the group consisting of titanium, aluminum, tin, zinc, magnesium and boron, and thereafter treating with a formyl amide of Formula XIV: ##STR44## where R.sup.2 is as defined above, and R.sup.5 and R.sup.6 are independently one of alkyl or alkaryl; or R.sup.5 and R.sup.6 when taken together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring, which may be optionally substituted, and which optionally may include an additional oxygen or nitrogen atom, to form an adduct of Formula II: ##STR45## where R.sup.1 through R.sup.6 are as defined above; c) catalytically hydrogenating said adduct of Formula II to form a .gamma.-lactam of Formula IV: ##STR46## where R.sup.1, R.sup.2 and R.sup.3 are as defined above; and d) saponifying said .gamma.-lactam of Formula IV to form a carboxylic acid of Formula V.