4-Nitropyridine, a key intermediate in medicinal products, was successfully prepared from pyridine N-oxide in a two-step -approach. Pyridine N-oxide was nitrated with HNO3 and H2SO4 to give 4-nitropyridine N-oxide, followed by reaction with PCl3 to give the final product. The continuous flow methodology was used to minimise accumulation of the highly energetic and potentially explosive nitration product to enable the safe scale-up of 4-nitropyridine with no 2-nitropyridine by-product. By employing continuous extraction in the nitration step and applying the optimised conditions, a throughput of 0.716 kg 4-nitropyridine product per day from pyridine N-oxide with 83% yield and high selectivity in a continuous flow system was achieved.

中文翻译：

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4-硝基吡啶的两步连续流动合成

以吡啶N-氧化物为原料，通过两步法成功制备了医药产品中的关键中间体4-硝基吡啶。吡啶N-氧化物用HNO3和H2SO4硝化得到4-硝基吡啶N-氧化物，然后与PCl3反应得到最终产物。连续流方法用于最大限度地减少高能量和潜在爆炸性硝化产物的积累，以实现 4-硝基吡啶的安全放大，而不会产生 2-硝基吡啶副产物。通过在硝化步骤中采用连续萃取并应用优化的条件，在连续流动系统中实现了每天从吡啶 N-氧化物中提取 0.716 kg 4-硝基吡啶产品的产量和 83% 的产率和高选择性。