405230-80-0

89510-90-7

General procedure for the synthesis of 2-chloro-5-fluoro-4-aminopyridine (12) from 2-chloro-5-fluoro-4-nitropyridine-1-oxide (11,1.3 g, 6.8 mmol): a mixture of the feedstock and 1.6 g of nickel ruanide in 80 mL of anhydrous ethanol was subjected to hydrogenation in a Parr hydrogenation unit under hydrogen pressure of 40 psi. The reaction process was monitored by thin layer chromatography (TLC) with the unfolding agent CH2Cl2/EtOAc (4:1, v/v) and the Rf values of the feedstock and the product were 0.78 and 0.71, respectively.The reaction lasted for 3 hr when the TLC showed that the feedstock disappeared and new spots were detected. After completion of the reaction, the catalyst was removed by filtration and washed carefully with ethanol. The filtrate and washings were combined and concentrated by vacuum evaporation to give 0.9 g (91% yield) of off-white solid product. A small amount of the sample was purified by recrystallization from hot water to give white crystals with a melting point of 110-111 °C. The 1H NMR (CDCl3) data of the product were as follows: δ 4.50 (br s, 2H, NH2, D2O exchangeable), 7.15 (d, 1H, 3-H, J = 6Hz), 7.95 (d, 1H, 6-H, J = 2Hz). Elemental analysis results (C5H4ClFN2) Calculated values: C, 40.97; H, 2.75; N, 19.12. Measured values: C, 41.18; H, 2.39; N, 18.89.