Scalable Preparation of Substituted 4-Aminoquinolines: Advancements in Manufacturing Process Development

We report herein an unprecedented and scalable synthetic method for the production of specific aminoquinoline compounds with potential applications as sweetness-enhancing agents. The first strategy involves the reaction of ortho-aminobenzonitriles with beta-ketoesters in the presence of stoichiometric amounts of FeCl3. Alternatively, the second strategy focuses on an enamine synthesis using alkyl acetoacetate and aminobenzonitrile. The resulting enaminonitrile is then converted into aminoquinoline under basic conditions. This newly developed process yields the desired compounds with an overall yield above 45 % over five steps with high purity.