MODERATE, HIGH-YIELD PROCESS OF N-(4-HYDROXYPHENYL)-RETINAMIDE SYNTHESIS IN LARGE SCALE AND PROCESSES FOR EMPLOYING INTERMEDIATES THEREFOR

摘要

This invention is directed to an efficient, mild, high yield process for the large scale synthesis of N-(4-hydroxyphenyl)-retinamide comprising the preferred steps of reacting retinoic acid with dimethylchloroformamidinium chloride to from retinoyl chloride which in turn is reacted with bis-(N,O)-trimethylsilyl-p-aminophenol to eventually form N-(4-hydroxyphenyl)-retinamide and to the novel use of bis-(N,O)-trimethylsilyl-p-aminophenol to eventually form a hydroxyphenylamide, particularly N-(4-hydroxyphenylretinamide and methods of recrystallizing N-(4-hydroxyphenyl)-retinamide to obtain the stable "A" polymorph thereof.