Patent ID: 6566553
Filing Date: 2003-05-20
Classification: A61P,C07B,C07C,C07D

Abstract:
A process for forming an enantiomerically-enriched formyl amide of Formula XIV: or a salt thereof, whereinR2 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; R5 and R6 are independently one of alkyl or alkaryl; or R5 and R6 when taken together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring, which can be optionally substituted, and which optionally include an additional oxygen or nitrogen atom; said method comprising:(a) acylating an anion of a compound of Formula VIII: where R8 is isopropyl or benzyl, with R2CH2COCl to form an acyloxazolidinone of Formula IX: where R2 and R8 are as defined above; (b) stereoselectively reacting the acyloxazolidinone of Formula IX with benzyloxymethyl chloride to form a protected alcohol of Formula X: where R2 and R8 are as defined above; (c) hydrolyzing the protected alcohol of Formula X to form a carboxylic acid of Formula XI: where R2 is as defined above; (d) coupling said acid of Formula XI with an amine R5R6NH2 to provide an amide of Formula XII: where R2, R5 and R6 are as defined above; (e) catalytically hydrogenating, the amide of Formula XII to form an alcohol of Formula XIII: where R2, R5 and R6 are as defined above; and (f) oxidizing the resultant alcohol of Formula XIII to give a formyl amide of Formula XIV.