Further studies on the synthesis of symmetrical anhydrides and 2,4-disubstituted-5(4H)-oxazolones from N-alkoxycarbonylamino acids using soluble carbodiimide

Abstract

Pure symmetrical anhydrides of N-alkoxycarbonyl (ROCO)-valine, for R = ethyl, tert-butyl, trichloroethyl, p-nitrobenzyl, p-methoxybenzyl, and 9-fluorenylmethyl, and N-ethoxycarbonylaminoisobutyric acid have been prepared using 0.5 equivalents of N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride in dichloromethane followed by removal of side-products by washing with aqueous solutions. When an excess of carbodiimide was used, 2-alkoxy-5(4H)-oxazolone was also generated, except when R = trichloroethyl. High yields of pure 5(4H)-oxazolone were obtained when R = ethyl. The 2-(9-fluorenylmethyloxy)-5(4H)-oxazolone gradually underwent a β-elimination during manipulation or storage.