Ammonium Chloride → 5-[4-(1-hydroxycyclobutyl)phenyl]-6-methyl-1H-indole-3-carbaldehyde

Participants

Reaction Steps

A mixture of dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphane (62.8 mg, 0.153 mmol), palladium acetate (13.7 mg, 0.061 mmol), tribasic potassium phosphate monohydrate (566 mg, 2.46 mmol), and methyl boronic acid (184 mg, 3.07 mmol) was sealed in a microwave tube and evacuated and backfilled with nitrogen three times. Deoxygenated 1,4-dioxane (1.5 mL) was added and the mixture was stirred vigorously at room temperature for one hour. A solution of 6-chloro-5-[4-(1-hydroxy-cyclobutyl)-phenyl]-1H-indole-3-carbaldehyde (400 mg, 1.23 mmol) in 1,4-dioxane (2.5 mL) was degassed with nitrogen for 10 minutes then added to the reaction mixture. The reaction mixture was heated at 120° C. for three hours under microwave irradiation, and then allowed to stir at room temperature for 12 hours. The reaction mixture was poured into saturated ammonium chloride solution (20 mL) and extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and evaporated. Flash silica gel chromatography was performed on the crude product utilizing a solvent system of heptanes/ethyl acetate (9:1 to 1:1) to give the title compound. MS (ES+) 306.5 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 9.86 (s, 1H), 8.06 (s, 1H), 7.95 (s, 1H), 7.55 (d, 2H), 7.38 (s, 1H), 7.36 (d, 2H), 2.61 (m, 2H), 2.39 (m, 2H), 2.34 (s, 3H), 2.05 (m, 1H), 1.75 (m, 1H).

Provenance & Evidence