Ethanol → Methyl 6-chloro-5-(4-(2-hydroxyethoxy)phenyl)-1H-indole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of methyl 5-bromo-6-chloro-1H-indole-3-carboxylate (5.2 g, 18.0 mmol), 2-(4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenoxy)ethanol (5.7 g, 22.8 mmol), PdCl2(dppf) (0.54 g, 0.72 mmol), 2 M aqueous solution of potassium carbonate (27 ml, 54.0 mmol), ethanol (30 ml), and toluene (90 ml) was stirred in a closed bottle at 80° C. for 2 hours and at 90° C. for 2 more hours. The reaction mixture was cooled to room temperature, ethyl acetate (50 ml) was added, and the mixture was filtered through a pad of Celite. The organic phase of the mother liquor was separated. Filter cake was washed with 10% of methanol in THF and this wash was combined with the first organic extract. The combined organic solution was dried over anhydrous magnesium sulfate and loaded on silica gel. Chromatography on a silica gel column, eluting with a gradient from 40% to 90% of ethyl acetate in heptanes to give the title compound (6.15 g, 98%). MS (ES+) 346.0 (M+1)+. 1H NMR (CDCl3): δ 8.74 (br. s, 1H), 8.13 (s, 1H), 7.95 (d, J=2.4 Hz, 1H), 7.56 (s, 1H), 7.44 (d, J=8.5 Hz, 2H), 7.02 (d, J=8.5 Hz, 2H), 4.18 (t, 2H), 4.02 (t, 2H), 3.92 (s, 3H).

Provenance & Evidence