N-Phenethyl-4-piperidinone

N-Phenethyl-4-piperidinone (NPP) is a derivative of 4-piperidinone with the molecular formula C₁₃H₁₇NO. It is used as an intermediate in the manufacture of chemicals and pharmaceutical drugs such as fentanyl.

N-Phenethyl-4-piperidinone

Names
Preferred IUPAC name 1-(2-Phenylethyl)piperidin-4-one
Other names 1-Phenethylpiperidin-4-one (no longer recommended) N-Phenylethyl-4-piperidinone N-Phenethyl-4-piperidone
Identifiers
CAS Number	39742-60-4 Y
3D model (JSmol)	Interactive image
Abbreviations	NPP
ChemSpider	87058 Y
ECHA InfoCard	100.049.630
PubChem CID	96437
UNII	CIS0S4O95K Y
CompTox Dashboard (EPA)	DTXSID30192826
InChI InChI=1S/C13H17NO/c15-13-7-10-14(11-8-13)9-6-12-4-2-1-3-5-12/h1-5H,6-11H2 Y Key: YDJXNYNKKXZBMP-UHFFFAOYSA-N Y InChI=1/C13H17NO/c15-13-7-10-14(11-8-13)9-6-12-4-2-1-3-5-12/h1-5H,6-11H2 Key: YDJXNYNKKXZBMP-UHFFFAOYAQ
SMILES O=C2CCN(CCc1ccccc1)CC2
Properties
Chemical formula	C13H17NO
Molar mass	203.28 g/mol
Density	1.057 g/cm3
Melting point	56 to 60 °C (133 to 140 °F; 329 to 333 K)
Hazards
GHS labelling:[1]
Pictograms
Signal word	Warning
Hazard statements	H302
Precautionary statements	P264, P270
NFPA 704 (fire diamond)	1 3
Legal status	AU: S9 (Prohibited substance) BR: Class D1 (Drug precursors)[2]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Because of its possible use in the illicit manufacture of fentanyl, the United States Drug Enforcement Administration (DEA) placed NPP under control as a List 1 Chemical in 2007. Both domestic sales and domestic importations are thus subject to DEA reporting requirements.^[3]

Preparation

N-Phenethyl-4-piperidinone can be prepared from 4-piperidinone and phenethyl bromide in biphasic conditions with a variety of phase transfer catalysts.^{[citation needed]}

Uses

N-Phenethyl-4-piperidinone is useful in the synthesis of addictive drugs, primarily fentanyl and its analogs. Paul Janssen (founder of Janssen Pharmaceutica) first synthesized fentanyl in 1960 from Benzylfentanyl.^[4] The Siegfried method (shown below and published on The Hive) involves reacting N-phenethyl-4-piperidinone with aniline, and then reducing the imine product with sodium borohydride to 4-anilino-N-phenethylpiperidine (ANPP). This product is reacted with propionyl chloride to form fentanyl.

References

1. GHS: PubChem
2. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
3. DEA Chemical Handler's Manual: A Guide to Chemical Control Regulations (2022 ed.). United States Department of Justice Drug Enforcement Administration Office of Diversion Control. May 9, 2014.
4. Schulz W. "Fentanyl". List of Top Pharmaceuticals. Chemical & Engineering News.

Further reading

• Beckett AH, Casy AF, Kirk G (February 1959). "Alpha- and beta-prodine type compounds". Journal of Medicinal and Pharmaceutical Chemistry. 1 (1): 37–58. doi:10.1021/jm50002a004. PMID 13655028. S2CID 42058755.