A mild and readily scalable procedure for the N-1-difluoromethylation of ethyl 6-((tert-butyldiphenylsilyl)oxy)-1H-indazole-3-carboxylate and its applications to the N-difluoromethylation of indazole, benzotriazole, imidazole, indole and pyrazole derivatives

[Display omitted] •Mild condition.•Scalable.•Suitable for substartes bearing labile groups. 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.