Amodiaquine dihydrochloride dihydrate (3) was prepared via a 4 step synthetic scheme involving a Mannich reaction, followed by hydrolysis of the amide group and a subsequent condensation with 4,7-dichloroquinoline (5). The key intermediate 14, was prepared by subjecting 4-acetamidophenol (13) to a Mannich reaction with diethylamine (DEA) and paraformaldehyde in a solvent. Several reaction conditions were attempted before achieving a robust method to obtain the Mannich base ( ) in desirable yields.