Synthesis
General procedure for the synthesis of 2-phenyl-3-aminopyridine from 3-amino-2-chloropyridine and phenylboronic acid: palladium acetate (224.5 mg, 1.00 mmol) and triphenylphosphine (1.05 g, 4.00 mmol) were dissolved in toluene (1000 mL) and stirred for 15 min at room temperature. Subsequently, phenylboronic acid (114 g, 935 mmol), 2-chloro-3-aminopyridine (100 g, 778 mmol), benzaldehyde (83.4 g, 786 mmol) and additional toluene (500 mL) were added to the reaction system. Next, a solution prepared from sodium carbonate (200 g, 1.89 mol) dissolved in water (1500 mL) was added. The reaction mixture was heated to reflux and maintained for 18 hours and then cooled to room temperature. Upon completion of the reaction, the organic and aqueous layers were separated. The organic layer was washed with water (500 mL) and subsequently acidified by adding 2.5 M aqueous hydrochloric acid (630 mL). The aqueous layer was separated and washed with toluene (300 mL). The pH of the aqueous layer was adjusted to 12-13 using 50% aqueous sodium hydroxide, followed by extraction with methyl tert-butyl ether (500 mL). The organic layers were combined, concentrated and the target product 2-phenyl-3-aminopyridine (128 g, 97% yield) was obtained by crystallization from diisopropyl ether. The melting point was determined to be 67-68 °C. 1H NMR (300 MHz, CDCl3) δ 3.88 (broad peak, 2H), 7.02-7.11 (multiple peaks, 2H), 7.28-7.53 (multiple peaks, 3H), 7.67-7.71 (multiple peaks, 2H), 8.13-8.16 (multiple peaks, 1H). 13C NMR (100 MHz. CDCl3) δ 122.57, 122.96, 128.14, 128.38, 128.72, 138.54, 139.86, 139.93, 144.93.
References
[1] Journal of Organic Chemistry, 2003, vol. 68, # 24, p. 9412 - 9415
[2] Patent: US6316632, 2001, B1
[3] European Journal of Organic Chemistry, 2012, # 31, p. 6248 - 6259,12
[4] European Journal of Organic Chemistry, 2012, # 31, p. 6248 - 6259
[5] Tetrahedron Letters, 2005, vol. 46, # 20, p. 3573 - 3577
