4-Chloro-pyridine-2-carbonitrile

Chemical Properties

Type of white solid

Uses

Substrate used to prepare chiral dialkylaminopyridines bearing a C-2 hydroxyalkyl group via biocatalysis.

Synthesis

4-Chloropyridine N-oxide (7.53 g, 58.1 mmol) and N,N-dimethylcarbamoyl chloride (9.36 g, 87.0 mmol) were mixed in acetonitrile (200 mL). Subsequently, trimethylcyanosilane (11.5 g, 116 mmol) was added slowly and dropwise to the reaction system. The reaction mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the mixture was combined with ethyl acetate and water for extraction. The organic layer was washed sequentially with saturated aqueous sodium bicarbonate and saturated saline, and then dried with magnesium sulfate. The solvent was removed by distillation and the residue obtained was purified by column chromatography (silica gel 200 g) using hexane-ethyl acetate (3:1, v/v) as eluent. The target fraction was collected and concentrated to give 4-chloro-2-cyanopyridine (8.05 g, 99% yield) as a light yellow oil. The product was characterized by 1H-NMR (CDCl3) and IR (KBr): 1H-NMR δ 7.54-7.56 (1H, m), 7.72 (1H, s), 8.63 (1H, d, J = 5.3 Hz); IR 2239, 1568, 1549, 1462, 1379, 1288, 1215, 844, 704 cm-1.

References

[1] Patent: EP1424336, 2004, A1. Location in patent: Page 219
[2] Patent: US2006/160803, 2006, A1. Location in patent: Page/Page column 146
[3] Tetrahedron Asymmetry, 2005, vol. 16, # 20, p. 3427 - 3435
[4] Patent: WO2005/95326, 2005, A2. Location in patent: Page/Page column 225-226
[5] Patent: WO2005/87215, 2005, A1. Location in patent: Page/Page column 143