4-ANPP, also known as 4-anilino-N-phenethylpiperidine (4-ANPP), 4-aminophenyl-1-phenethylpiperidine, or despropionyl fentanyl,[1] is a direct precursor to fentanyl and acetylfentanyl. It is commonly found as a contaminant in samples of drugs containing fentanyl, which may include samples represented by the supplier as heroin or other opioids.[2] It is not psychoactive and is present only as a result of improper chemical purification.
4-ANPP can be prepared from N-phenethyl-4-piperidinone (NPP) and aniline, then being reduced.
4-ANPP can also be prepared using 4-anilinopiperidine and selectively adding the phenethyl group.
4-ANPP is useful in the synthesis of pharmaceuticals, primarily fentanyl and related analogs. Paul Janssen (founder of Janssen Pharmaceutica) first synthesized fentanyl in 1960 using a similar method, with Benzylfentanyl as an intermediate.[3] The following synthesis, developed by an individual under the pseudonym of Siegfried, involves the reductive amination of N-phenethyl-4-piperidinone (NPP) to 4-ANPP. This product is reacted with propionyl chloride or acetyl chloride to form either fentanyl or acetylfentanyl.