4-ANPP, also known as 4-anilino-''N''-phenethylpiperidine (4-ANPP), 4-aminophenyl-1-phenethylpiperidine, or despropionyl fentanyl, is a direct precursor to

fentanyl Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...

and some fentanyl analogues such as 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. It is not psychoactive and is present only as a result of improper processing of the intended product of the synthesis.

Preparation

4-ANPP can be prepared from ''N''-phenethyl-4-piperidinone (NPP) and

aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...

, then being reduced. 4-ANPP can also be prepared using 4-anilinopiperidine and selectively adding the phenethyl group.

Uses

4-ANPP is useful in the synthesis of pharmaceuticals, primarily fentanyl and its analogs.

Paul Janssen Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson. Ea ...

(founder of

Janssen Pharmaceutica Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American ...

) first synthesized fentanyl in 1960 using 4-ANPP as an intermediate. Janssen's synthesis involved reacting ''N''-phenethyl-4-piperidinone (NPP) with aniline, and then reducing the imine product with

sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...

to 4-ANPP. This product is reacted with propionyl chloride to form

. :

References

{{reflist Piperidines Phenethylamines Janssen Pharmaceutica