Potassium Carbonate → 6-chloro-5-(4-(3-hydroxyoxetan-3-yl)phenyl)-1H-indole-3-carbaldehyde

Participants

Reaction Conditions

Reaction Steps

A mixture of 5,5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] (149.0 mg, 0.44 mmol), oven dried potassium acetate (173.0 mg, 1.75 mmol) and 3-(4-bromo-phenyl)-oxetan-3-ol (100.0 mg, 0.44 mmol) in 1,4-dioxane (2 mL) was degassed with N2 for 5 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (33.0 mg, 0.044 mmol) and subjected to microwave irradiation at 110° C. for 1 hour. The cooled reaction mixture was filtered through celite and concentrated in vacuo to give a black oil. To the dark oil was added 5-bromo-6-chloro-1H-indole-3-carbaldehyde (112.0 mg, 0.43 mmol), 2 N aqueous potassium carbonate (0.4 mL, 0.80 mmol), toluene (1.5 mL) and EtOH (0.5 mL). The reaction mixture was degassed with N2 for 10 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (25.0 mg, 0.034 mmol), and heated in a pressure tube to 110° C. for 2 hours. The cooled reaction mixture was purified by flash chromatography (33-100% EtOAc/heptanes) to give a solid. The solid was triturated in MeOH and filtered to afford the title compound (50 mg, 35%) as a yellow solid. MS (ES+) 328.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.23 (s, 1 H), 9.92 (s, 1 H), 8.35 (s, 1 H), 8.02 (s, 1 H), 7.66 (d, J=9.4 Hz, 2 H), 7.44 (d, J=8.2 Hz, 2 H), 6.36 (s, 1 H), 4.80-4.76 (m, 2 H), 4.75-4.71 (m, 2 H).

Provenance & Evidence