Cyanoacetamide → 4-Cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile

To a stirred suspension of CrCl2 (58 g, 472.8 mmol) in THF (1500 mL) was added a THF solution (500 mL) of 1,1-dichloro-2-propanone 10 g, 78.8 mmol) and cyclohexanecarbaldehyde (8.84 g, 78.8 mmol). The reaction mixture was heated at reflux for 2 h, and then quenched by the addition of 1.0 M HCl. The reaction mixture was filtered through a pad of Celite and concentrated in vacuo. The crude residue (10 g) was added to a solution of DMSO (150 mL) containing t-BuOK (7.5 g, 65.7 mmol) and cyanoacetamide (6.1 g, 72.3 mmol) and stirred at room temperature for 30 min. Additional t-BuOK (22.5 g, 197.1 mmol) was added and the reaction mixture was stirred under an atmosphere of oxygen for an additional 1 h. The contents were purged with argon, diluted with 4 volumes of H2O, and then 5 volumes of 4 N HCl, which were added slowly. The reaction mixture was filtered, washed with water and dried to give 4-cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (4.5 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.25 (s, 1H), 2.61-2.65 (m, 1H), 2.22 (s, 3H), 1.66-1.79 (m, 4H), 1.24-1.46 (m, 6H).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 2 h
3. customquenched by the addition of 1.0 M HCl
4. filtrationThe reaction mixture was filtered through a pad of Celite
5. concentrationconcentrated in vacuo
6. additionThe crude residue (10 g) was added to a solution of DMSO (150 mL)
7. stirringthe reaction mixture was stirred under an atmosphere of oxygen for an additional 1 h
8. customThe contents were purged with argon
9. additiondiluted with 4 volumes of H2O
10. addition5 volumes of 4 N HCl, which were added slowly
11. filtrationThe reaction mixture was filtered
12. washwashed with water
13. customdried

ORDレコード

ord-7f7745400f644c519d76aa2dc66e6d8a

出典データセット

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08536179B2