4-Hydroxypyridine (300 g, 3.15 mol, 1 wt) was added in batches to a 20 L flask containing concentrated sulfuric acid (1500 mL, 5 vol) under nitrogen protection. The nitration mixture was prepared by slowly adding concentrated nitric acid to concentrated sulfuric acid and under stirring. Subsequently, the nitrification mixture was cautiously transferred to a 20 L reactor. The reaction mixture was heated at 60°C to 70°C for 3 hours and subsequently cooled to room temperature over a period of 16 hours. The reaction mixture was poured into 10 L of ice water. The mixture was alkalized to pH 11-12 by dropwise addition of concentrated ammonia (8000 mL, 26.7 vol).The reaction mixture was concentrated under reduced pressure and the residue was stirred in pyridine (10000 mL, 33 vol) and filtered. The inorganic solid was dissolved in water (10000 mL, 33 vol) and extracted three times with pyridine (3 x 2500 mL, 3 x 8.3 vol), the pyridine extracts were combined and concentrated. The residue was stirred in acetone (6600 mL, 22 vol) for 1.5 h. It was filtered and dried over 16 h to give 716.1 g of crude product. The crude product, 4-hydroxy-3-nitropyridine (623.6 g), was slurried in water (1250 mL, 2 vol) for 60 min to remove residual inorganics. The slurry was filtered and dried for 72 h to give 4-hydroxy-3-nitropyridine (334.4 g, 76% yield, KF: 0.25%).1H NMR (400 MHz, DMSO): δ 6.58 (d, J = 6 Hz, 1H), 7.85 (d, J = 6 Hz, 1H), 8.88 (s, 1H).
