Hydrochloric Acid → (2-Aminophenyl)(pyridin-4-yl)methanone

Alternatively, to a solution of 1-iodo-2-nitrobenzene (3.76 g, 15.1 mmol) in dry THF (80 mL) at −78° C. was added n-butyl lithium (7.54 mL, 18.9 mmol) over 5 min. After 40 min at −78° C., ethyl isonicotinate was added in one portion in dry THF (70 mL). After 10 min, the reaction was allowed to warm to 0° C. for 10 min then quenched with 20 mL of glacial acetic acid: 30 mL of water. After adjusting the pH to 8 with saturated bicarbonate solution, the mixture was extracted with ethyl acetate (1×500 mL), washed with brine (2×500 mL), dried (Na2SO4). After concentration in vacuo, the reaction mixture was treated with 120 mL of 5 N NaOH:methanol:water (1:1:1). After removal of methanol in vacuo, the reaction mixture was extracted with ethyl acetate (1×500 mL), then dried (Na2SO4). After concentration in vacuo, the residue was purified by applying flash chromatography (step gradient methylene chloride 100%; the 20% ethyl acetate:methylene chloride: then 40% ethyl acetate:methylene chloride) to afford 4-(2-nitobenzoyl)pyridine. 4-(2-Nitrobenzoyl)pyridine (100 mg, 0.44 mmol), stannous chloride dihydrate (297 mg, 1.32 mmol), and 1.1 mL of concentrated hydrochloric acid were warmed to 100° C. for 10 minutes. After cooling to 23° C., the reaction was poured into water (10 mL) and 5 N sodium hydroxide (14 mL) followed by extraction with ethyl acetate (2×50 mL). The ethyl acetate layer was washed with brine (1×20 mL), dried (Na2SO4), and concentrated in vacuo to afford 4-(2-aminobenzoyl)pyridine (12).