5-Fluoro-1H-indole-7-carboxaldehyde (0041) was synthesized as follows: vinylmagnesium bromide (1M tetrahydrofuran solution, 85.2 mL, 85.2 mmol) was slowly added dropwise to a solution of 2-dibutoxymethyl-4-fluoro-1-nitrobenzene (8.5 g, 28.4 mmol) in tetrahydrofuran (250 mL) at -78 °C. The reaction mixture was warmed at -45°C to -50°C for 30 min before being cooled again to -78°C and vinylmagnesium bromide (1 M solution in tetrahydrofuran, 85.2 mL, 85.2 mmol) was added dropwise. Subsequently, the mixture was kept at -45 °C to -50 °C for 20 min before the reaction was terminated by the addition of saturated aqueous ammonium chloride solution (300 mL). After warming the mixture to room temperature, it was extracted with ether (200 mL x 2). The combined organic phases were washed with saturated aqueous sodium chloride (400 mL x 2), dried over sodium sulfate and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (100 mL), 0.5N HCl (10 mL) was added and stirred for 20 min. The reaction mixture was diluted with ether (200 mL) and washed sequentially with saturated aqueous sodium bicarbonate solution (200 mL x 3) and saturated aqueous sodium chloride solution (200 mL x 2). The organic phase was dried over sodium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using 5% to 10% hexane solution of ethyl acetate as eluent to give a light yellow solid target product (2.6 g, 56% yield). The product was confirmed by 1H-NMR (300 MHz, CDCl3): δ 10.07 (s, 1H), 10.05 (br s, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.42-7.39 (m, 2H), 6.60 (d, J=5.4 Hz, 1H).
