Water → 1-Benzyl-4-(pyridin-2-yl)piperidine-4-carbonitrile

Temperatur

65 °C

To a mixture of N,N-bis-(2-chloroethyl)benzylamine (Szarvasi, E., Eur. J. Med. Chem. Chem. Ther. 11(2), 115-124, 1976) (60 g, 22 mmol), 2-pyridylacetonitrile (2.51 mL, 22 mmol) and tetrabutylammonium hydrogen sulfate (0.26 g, 0.7 mmol) in toluene (10 mL), sodium hydroxide solution (2.43 g in 4.86 mL H2O) was added over a 20 minute period. The reaction mixture was heated at 65° C. for 4 hours. The reaction mixture was cooled to room temperature, 10 mL of water was added and the solution partitioned between ethyl acetate (45 mL) and water. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification of the crude product by column chromatography (hexane: EtOAc, 2:3) gave 6.2 g (87%) of the title compound as a red solid; 1H-NMR (CDCl3): δ2.05 (d, J 13.1 Hz, 2H), 2.30 (t, J=13.2 Hz, 2H), 2.48 (t, J=13.2 Hz, 2 H), 2.97 (d, J=12.1 Hz, 2 H), 3.57 (s, 2 H), 7.19-7.27 (m, 6 H), 7.30 (d, J=7.6 Hz, 1 H), 7.60 (t, J=7.6 Hz, 1 H ), 8.58 (d, J=4.6 Hz, 1 H).

1. additionwas added over a 20 minute period
2. temperatureThe reaction mixture was cooled to room temperature
3. customthe solution partitioned between ethyl acetate (45 mL) and water
4. dry with materialThe organic layer was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification of the crude product by column chromatography (hexane: EtOAc, 2:3)

ORD-Eintrag

ord-2141d01177ac440e95c1341f6284f82a

Quelldatensatz

uspto-grants-2003_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06531471B2