Acetonitrile → HCID 10977406, compound

Participants

Reaction Steps

A mixture of 5-bromo-1-(4-fluorphenyl)-1H-indole (40 g) (prepared as described by Perregaard et al. J. Med. Chem. 1992 35, 1092-1101), (trimethylsilyl)acetylen (21.4 g), bis(triphenylphospine)palladium(II) dichloride (2.9 g) copper(I) iodide (1.3 g), triethylamine (40 mL) and acetonitrile (150 mL) was boiled under reflux for 8 hours. After cooling to room temperature, water was added and the resulting mixture was extracted with ethyl acetate (4×300 mL). The combined organic phases were washed with brine (2×800 mL), dried (Na2SO4) and the solvents evaporated in vacuo. A solution of the remaining oil and potassium hydroxide (12.1 g) in a mixture of methanol (500 mL) and water (200 mL) was boiled at reflux for 3 h. The volatile solvents were evaporated in vacuo and a mixture of water (200 mL) and ethyl acetate (1000 mL) was added. The phases were separated and the aqueous phase extracted with ethyl acetate (250 mL). The combined organic phases were dried (Na2SO4) and the volatile solvents evaporated in vacuo. Purification of the remaining oil by column chromatography on silica gel (dichloromethane/heptane 1:6) afforded crystalline pure title compound 18a (11.4 g): Sp 99-100° C.; 1H NMR (CDCl3) δ 3.00 (s, 1H), 6.55 (d, 1H), 7.20 (t, 2H), 7.25 (d, 1H), 7.35 (m, 2H), 7.40 (dd, 2H), 7.85 (broad s, 1H).

Provenance & Evidence