1-(6-Nitropyridin-3-yl)pyrrolidin-2-one synthesis

Yield:1019651-21-8 44%

Reaction Conditions:

with copper(l) iodide;caesium carbonate;palladium diacetate;4,5-bis(diphenylphosphino)-9,9-dimethylxanthene in toluene at 10 - 75; for 24 h;Inert atmosphere;

Steps:

81

Reference Example 81; 1-(6-aminopyridin-3-yl)pyrrolidin-2-oneA solution of palladium acetate (0.22 g, 1.0 mmol) and 5-bis(diphenylphosphino)-9,9-dimethylxanthine (0.58 g, 1.0 mmol) in toluene (30 mL) was stirred at room temperature for 15 min under an argon atmosphere. 5-Bromo-2-nitropyridine (1.0 g, 5.0 mmol), 2-pyrrolidone (0.64 g, 7.5 mmol), copper iodide(I) (0.19 g, 1.0 mmol) and cesium carbonate (2.4 g, 7.5 mmol) were added to the mixture, and the mixture was stirred at 75° C. for 24 hr. The reaction solution was filtered through glass filter (6.7 cm) in which silica gel (30 g) and ethyl acetate were charged to remove the insoluble material. The solvent was evaporated under reduced pressure, and the precipitated crystals were collected by filtration to give 1-(6-nitropyridin-3-yl)pyrrolidin-2-one (0.45 g, yield 44%) as pale-yellow crystals.¹H-NMR (400 MHz, CDCl₃) δ: 2.30 (2H, dt, J=15.2, 7.7 Hz), 2.71 (2H, t, J=8.2 Hz), 3.99 (2H, t, J=7.0 Hz), 8.30 (1H, d, J=8.8 Hz), 8.67 (1H, dd, J=8.8, 2.4 Hz), 8.72 (1H, d, J=2.7 Hz)

References:

US2011/39893,2011,A1 Location in patent:Page/Page column 34