Ethyl Acetate → methyl 5-(biphenyl-4-yl)-6-chloro-1H-indole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 5-bromo-6-chloro-1H-indole-3-carboxylate (150 mg, 0.52 mmol), 4-biphenylboronic acid (113 mg, 0.57 mmol) and 2M aqueous potassium carbonate (2M, 1.04 mL, 2.08 mmol) in toluene (3.0 mL) and ethanol (1.0 mL) was degassed with nitrogen for 10 minutes. The reaction mixture was then treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (20.0 mg, 0.026 mmol) and heated at 110° C. for 2 h in a sealed reaction vessel, which caused the reaction to appear burnt orange. The reaction mixture was cooled to room temperature and poured into ethyl acetate and water. The layers were separated and the aqueous layer was back-extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The material was then dissolved in ethyl acetate and methanol then silica gel was added. The solvent was removed and the crude material adsorbed onto silica gel was added to a column of silica gel and eluted with ethyl acetate/heptanes (1:4 to 1:1) to give the desired product as a tan solid 61 mg (35% yield). MS (ES+) 362.5 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.53 (br. s., 1H), 8.17 (s, 1H), 7.94 (d, J=2.15 Hz, 1H), 7.61-7.72 (m, 4H), 7.57 (d, J=6.05 Hz, 2H), 7.45 (t, J=7.61 Hz, 2H), 7.31-7.40 (m, 1H), 3.89 (s, 3H).

Provenance & Evidence