A set of mild conditions for the N-1-difluoromethylation of ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate (1) with chlorodifluoromethane (CHClF₂) on large scale (up to 33 g) is described. An optimized N-1-difluoromethylation of the functionalized indazole 1 was achieved, under an atmosphere of CHClF₂ (balloon) in the presence of NaH and catalytic amounts of NaI and 18-crown-6 ether at a moderate temperature (40 °C). This procedure provides a safe and convenient alternative to existing approaches that require high pressures and/or the use of NaH in DMF at high temperatures that would present a safety concern when operating on a large scale. This method was extended to the N-difluoromethylation of indazole, benzotriazole, imidazole, indole and pyrazole derivatives, all of which bear an ester group.

一组为温和条件Ñ（（叔丁基二苯基硅烷基）氧基）-1 - -1-二氟甲基乙基6的ħ -吲唑-3-羧酸甲酯（1）与氯二氟甲烷（CHClF ₂上大规模（向上）到33克）进行了说明。在CHClF ₂气氛下，对官能化的吲唑1进行了优化的N -1-二氟甲基化（气球）在适中的温度（40°C）下存在NaH和催化量的NaI和18-冠6醚。该程序为需要高压和/或在高温下在DMF中使用NaH的现有方法提供了一种安全方便的替代方法，这在大规模操作时会带来安全隐患。该方法扩展到吲哚，苯并三唑，咪唑，吲哚和吡唑衍生物的N-二氟甲基化，所有这些均带有酯基。