Potassium Carbonate → 6-Chloro-5-(4-(1-hydroxycyclobutyl)phenyl)-1H-indole-3-carbaldehyde

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A mixture of 5-bromo-6-chloro-1H-indole-3-carbaldehyde (6.15 g, 23.8 mmol), 1-[4-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-phenyl]-cyclobutanol (8.35 g, 32.1 mmol), 2M aqueous potassium carbonate (47.5 mL, 95.0 mmol) in EtOH (33 mL) and toluene (86 mL) was degassed with N2 for 25 minutes, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1.93 g, 2.64 mmol). The reaction mixture was heated to 110° C. and stirred for 2 hours. The reaction mixture was cooled to room temperature, poured into a 3:1 mixture of saturated aqueous NH4Cl solution/water (450 mL) and extracted with EtOAc (10×150 mL), followed by 9:1 CH2Cl2/i-PrOH (4×100 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (0-100% EtOAc/heptane, with 0.03% formic acid modifier) to afford the title compound (4.98 g, 64%) as a red solid. MS (ES+) 326.5 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.21 (br. s., 1H), 9.91 (s, 1H), 8.35 (s, 1H), 8.02 (s, 1H), 7.67 (s, 1H), 7.54 (d, J=8.00 Hz, 2H), 7.38 (d, J=8.20 Hz, 2H), 5.50 (s, 1H), 2.36-2.45 (m, 2H), 2.22-2.33 (m, 2H), 1.92 (m, 1H), 1.61-1.71 (m, 1H).

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