The difluoromethylation of methyl 4-hydroxy-3-iodobenzoate has been demonstrated on multikilogram scale. Prior to execution, several issues had to be addressed. First, the difluorocarbene source had to be explored to avoid using highly toxic gases such as chlorodifluoromethane. After choosing sodium chlorodifluoroacetate as the difluororcarbene precursor and potassium carbonate as the base, a safety evaluation had to be performed to ensure this transformation could be carried out safely on multikilogram scale. Herein, we report a safe and practical difluoromethylation protocol of methyl 4-hydroxy-3-iodobenzoate. This procedure was successfully implemented on 7 kg scale to produce (6) in 99% yield and 99% purity after crystallization.

中文翻译：

---

4-羟基-3-碘代苯甲酸甲酯的二氟甲基化的安全实用方法

4-羟基-3-碘苯甲酸甲酯的二氟甲基化已在多千克规模上得到证明。在执行之前，必须解决几个问题。首先，必须探索二氟卡宾的来源，以避免使用剧毒的气体，例如氯二氟甲烷。在选择氯二氟乙酸钠作为二氟卡宾前体和碳酸钾作为碱之后，必须进行安全性评估，以确保可以在多千克规模上安全地进行该转化。在此，我们报告了4-羟基-3-碘苯甲酸甲酯的安全实用的二氟甲基化方案。该步骤成功地以7 kg规模实施，结晶后以99％的收率和99％的纯度生产（6）。