title: Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives.
abstract: Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N-hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 °C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials.
authors: Department of Chemistry, State University of New York at Stony Brook; Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook.
authors: Pengju
authors: P
authors: Feng
authors: Department of Chemistry, State University of New York at Stony Brook; Institute of Chemical Biology and Drug Discovery, State University of New York at Stony Brook; ming-yu.ngai@stonybrook.edu.
authors: Ming-Yu
authors: MY
authors: Ngai
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis*; D002384:Catalysis; D060326:Chemistry Techniques, Synthetic / Q000379:methods; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis
chemical_list: D000814:Aniline Compounds; D006845:Hydrocarbons, Fluorinated