Synthesis
General procedure for the synthesis of 4-chloro-6-fluoro-1H-indole from vinyl acetate and compound (CAS: 1431711-55-5): (c) 4-chloro-6-fluoro-1H-indole N-(3-chloro-5-fluoro-phenyl)-N-hydroxy-acetamide (200 mg, 982 μmol) was dissolved in vinyl acetate (1.81 mL, 19.6 mmol) in vinyl acetate (1.81 mL, 19.6 mmol), followed by addition of Li2PdCl4 (25.7 mg, 98 μmol). The reaction mixture was stirred at 60 °C for 3 hours. After completion of the reaction, the reaction mixture was diluted with ethyl acetate (EtOAc) and brine; the organic layer was separated and concentrated under reduced pressure to obtain a solid. The solid was dissolved in 8 mL of methanol (MeOH), 1N aqueous sodium hydroxide solution (1.89 mL, 1.89 mmol) was added, and stirred at room temperature for 2 hours. The reaction mixture was quenched with 2N aqueous hydrochloric acid (0.95 mL, 1.9 mmol) followed by the addition of 300 mg of sodium carbonate (Na2CO3). After addition of 50 mL of ethyl acetate (EtOAc), the organic layer was separated, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (12 g silica gel (SiO2); ethyl acetate/heptane, gradient from 0/100 to 1/4) to afford the title compound as a liquid (72 mg, 45% yield, two steps).1H-NMR (DMSO-d6): δ 11.52 (brs, 1H), 7.45 (d, 1H), 7.20 (d, 1H), 7.05 (d, 1H), 6.45 (d, 1H).
