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

Participants

Reaction Conditions

Reaction Steps

A mixture of 5,5,5′,5′-tetramethyl-2,2′-bi(1,3,2-dioxaborinane) (188.0 mg, 0.55 mmol), oven dried potassium acetate (230.0 mg, 2.34 mmol), and 1-(4-bromophenyl)cyclobutanol (114.0 mg, 0.50 mmol) in 1,4-dioxane (2 mL) was degassed with N2 for 15 min, then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (20.0 mg, 0.027 mmol). The reaction mixture was subjected to microwave irradiation at 110° C. for 1 hour. The cooled reaction mixture was filtered through celite, rinsed with EtOAc and concentrated to dryness. To the resulting dark solid ((45.0 mg, 0.17 mmol) was added 5-bromo-4,6-difluoro-1H-indole-3-carbaldehyde (45.0 mg, 0.17 mmol), 2N aqueous potassium carbonate (0.20 mL, 0.40 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) (14.0 mg, 0.019 mmol), and heated in a sealed pressure tube at 110° C. for 2 hours. The reaction mixture was cooled to room temperature and purified by flash chromatography (0-67% EtOAc/heptanes) to give the title compound (37 mg, 65%) as a white solid. MS (ES+) 328.0 (M+H)+. 1H NMR (500 MHz, CD3OD) δ 10.04 (d, J=2.68 Hz, 1H), 8.15 (s, 1H), 7.64 (d, J=8.05 Hz, 2H), 7.48 (d, J=8.05 Hz, 2H), 7.21 (d, J=9.51 Hz, 1H), 2.57-2.66 (m, 2H), 2.39-2.46 (m, 2H), 2.03-2.12 (m, 1H), 1.73-1.83 (m, 1H).

Provenance & Evidence