The continuous production of the intermediate ortho-4-(2-fluoro-4-nitrophenyl)morpholine (o-FNM) was firstly explored in Microfluidic devices. The o-FNM is a key intermediate to synthesize Linezolid, a highly effective active pharmaceutical used against a wide class of Gram-positive pathogens. It is synthesized by eight consecutive reactions, taking about 60 h. One of the most prolonged step, lasting about 11 h, is the reaction between morpholine and 2,4-difluoronitrobenzene to produce o-FNM. Despite these features, there is still a lack on researches approaching such process. The present paper evaluated for the first time the production of o-FNM in micro- and millireactors by CFD. An optimization of operating conditions (temperature, reactants molar ratio (MR) and residence time (τ)) was performed by a Central Composite Rotatable Design, evaluating its effects on the limiting reactant conversion, selectivity and production rate. The optimal production rate (157−195 mg/h in the microreactor) was noticed at 105 °C, MR = 4, τ = 50 s. The performance of different micromixer designs and scale-up effects was assessed. The devices exhibited o-FNM production rate about 1.5–7.5 g/h, equivalent to the reported in literature, keeping high levels of limiting reactant conversions (≈ 99 %) and considerable selectivities (≥ 10).

最初在微流体装置中研究了连续的中间体邻4-（2-氟-4-硝基苯基）吗啉（o-FNM）的生产。o-FNM是合成Linezolid（一种针对多种革兰氏阳性病原体的高效活性药物）的关键中间体。它由八个连续的反应合成，耗时约60小时。持续约11小时的最长时间的步骤之一是吗啉与2,4-二氟硝基苯之间的反应，生成邻位FNM。尽管具有这些特征，但仍缺乏进行这种过程的研究。本文首次评估了通过CFD在微型和毫微反应器中生产o-FNM的方法。通过中央复合旋转设计对操作条件（温度，反应物摩尔比（MR）和停留时间（τ））进行了优化，评估其对极限反应物转化率，选择性和生产率的影响。在105°C，MR = 4，τ= 50 s时，观察到最佳生产率（在微反应器中为157-195 mg / h）。评估了不同微混合器设计的性能和放大效果。该装置的邻-FNM生产率约为1.5-7.5 g / h，与文献报道的相当，保持了高水平的限制反应物转化率（≈99％）和相当高的选择性（≥10）。