7-(Trifluoromethoxy)-1H-indole

Synthesis

396075-92-6

396075-91-5

General procedure for the synthesis of 7-(trifluoromethoxy)-1H-indole from the compound (CAS: 396075-92-6): first, D-7-trifluoromethoxy-1H-indole KOH (1.95 g, 34.8 mmol) was dissolved in tertiary butanol (55 mL), heated to 80 °C and kept for 2 h until the solution became homogeneous and clarified. Subsequently, ethyl (2-trifluoromethoxy-6-trimethylsilylethynyl-phenyl)-carbamate (5.214 g, 15.1 mmol) was added to this solution and heating was continued at 80 °C for 2 hours. After completion of the reaction, the solvent was removed by vacuum distillation. The organic layer was separated by partitioning the residue between ether (Et2O) and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuum. The crude product was purified by silica gel column chromatography using ethyl acetate/heptane (1-5%) as eluent to give the final title product 7-(trifluoromethoxy)-1H-indole (1.82 g, 60% yield) as a yellow liquid. The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) δ 8.40 (br s, 1H), 7.58-7.55 (m, 1H), 7.25 (m, 1H), 7.09-7.07 (m, 2H), 6.62-6.60 (m, 1H); 19F NMR (300 MHz, CDCl3) δ -57.50 (s, 3F ) Confirmation. Elemental analysis (CHN) theoretical values: C 53.74%, H 3.01%, N 6.96%; measured values: C 53.86%, H 3.14%, N 6.97%.

References