Hydrogen Peroxide → 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)benzaldehyde

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Ex-15A: 1-Methylindole (5.0 g, 38.1 mmol) was dissolved in tetrahydrofuran (190 mL) and nitrogen was bubbled into the solution for 15 min. The solution was then cooled to 0° C. and tert-butyllithium (1.6 M solution in pentane, 23.5 mL, 40.0 mmol) was added dropwise and the mixture was stirred for 30 min at 0° C. and then warmed to room temperature and stirred for an additional 1 h. Triethylborane (1.0 M solution in THF, 45.7 mL, 45.7 mmol) was added, and the reaction mixture was stirred for 1 h at room temperature. To the crude indolylborate, generated in situ, was added 5-bromo-2,4-dimethoxybenzaldehyde (9.3 g, 38.1 mmol) and bis(tri-t-butylphosphine)palladium (0) (0.48 g, 0.95 mmol). The solution was immediately heated to 60° C. and aged for 30 min. Upon completion, as determined by HPLC, the reaction was treated with 10% aqueous sodium hydroxide (190 mL) and 30% hydrogen peroxide (38 mL) with ice-cooling for 20 min. The mixture was extracted with ethyl acetate (3×100 mL), and the combined organic extracts were washed with brine (2×75 mL), dried over sodium sulfate and concentrated to a brown oil. Silica gel chromatography (ethyl acetate/hexanes, 1:3 to 3:1) gave 7.69 g (77%) of 2,4-dimethoxy-5-(1-methyl-1H-indol-2-yl)benzaldehyde as a yellow solid, mp 153–153° C. 1H-NMR (300 MHz, CDCl3) δ 10.36 (s, 1H), 7.87 (s, 1H), 7.37 (d, 1H, J=7.5 Hz), 7.31 (d, 1H, J=9.0 Hz), 7.20–7.28 (m, 1H), 7.12 (t, 1H, J=6.8 Hz), 6.55 (s, 1H), 6.48 (s, 1H), 4.03 (s, 3H), 3.91 (s, 3H), 3.55 (s, 3H). Anal. Calcd. for C18H17NO3: C, 73.20; H, 5.80; N, 4.74; Found: C, 72.98; H, 5.89; N, 4.73.

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