1-Benzyl-3-methylpiperidin-4-one

clear slightly yellow to yellow liquid

To a solution of NaH (15 g, 0.38 mol, 60percent dispersion) in THF (600 niL) was added l-benzylpiperidin-4-one (60 g, 0.3 mol) in THF (100 niL) at 0(8-1) To a solution of 1-benzylpiperidin-4-one (5.50 g, 29.1 mmol) in THF (100 mL) was added NaH (1700 mg, 60percent in mineral oil, 43.7 mmol) at 0 °C. The resulting mixture was stirred at 0 °C for 30 minutes. To the resulting mixture was added Mel (6200 mg, 43.7 mmol) at 0 °C. After being heated with stirring at 60 °C overnight, the resulting reaction mixture was cooled to rt, diluted with sat. aqueous solution of NH4C1 (50 mL) and extracted with EA (50 mL) for three times. The combined organic layer was dried over anhydrous Na2504 and concentrated in vacuo. The residue was purified by flash column (eluting with 1percent MeOH in DCM) to give 1-benzyl-3- methyl-piperidin-4-one (2.50 g).Sodium hydride (4.20 g, 175.0 mmol) was suspended in THF (200 mL), and a solution of the piperidone (18.9 g, 99.9 mmol) and methyl iodide (17.9 g, 126.1 mmol) in THF (20 mL) was added dropwise at room temperature over 5 minutes. The mixture was then heated to 60 °C and stirred for 5 hours. The reaction was then filtered and the filtrate concentrated. The concentrate was poured into 150 mL of water and extracted with 120 mL portions of EtOAc three times. The extract was washed with brine, dried, and concentrated. The crude product was purified by column chromatography (gradient: 12percent EtOAc in hexanes to 50percent EtOAc in hexanes over 1200 mL). Both mono and di methylation occurred. Separation of both isomers by chromatography was quite facile. 3.53 g of the dimethylated product (16percent) was obtained. MS (EI) : m/z 218.1 (M + 1). 5.91 g (29percent) of the monomethylated product was obtained. MS (EI) : m/z 204.0 (M + 1).

A piperidine derivative used in the preparation of Fentanyl (F274990) analogs with analgesic activity.

Molecular Weight:203.28
XLogP3:1.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:203.131014166
Monoisotopic Mass:203.131014166
Topological Polar Surface Area:20.3
Heavy Atom Count:15
Complexity:221
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes