Water → HCID 70278038, compound

Participants

Reaction Steps

To a solution of 2-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyloxy]ethanol (2a) (4.8, 0.016 mol) and triethylamine (5 mL) in dichloromethane (50 mL), a solution of methanesulfonyl chloride (1.9 mL, 0.025 mol) in dichloromethane (16 mL) was added at 0°-5° C. over 0.5 h. After stirring for 3 h at room temperature the reaction mixture was washed with water (2×100 mL), dried (Na2SO4) and the solvents were evaporated in vacuo. Excess of methanesulfonyl chloride was removed by concentrating the remaining oil with toluene in vacuo several times. The crude methanesulfonate of 2a (6.0 g, 0.016 mol) was used without further purification. A mixture of the crude methanesulfonate, 2-(methylamino)ethyl-2-imidazolidinone (4.9 g, 0.034 mol), K2 CO3 (4.0 g, 0.029 mol) and methyl isobutyl ketone was refluxed for 18 h. After cooling to room temperature water (100 mL) was added and the resulting mixture was extracted with ethyl acetate (2×100 mL). The combined organic phases were washed with water (100 mL) and brine (100 mL), and dried (Na2SO4). Evaporation of the solvents and purification by column chromatography on silica gel (eluted with ethyl acetate/ethanol 5:1 containing 4% triethylamine) afforded the title compound (4.2 g, 61%) as an oil. The title compound crystallized as its maleate from ethyl acetate: mp 183°-185° C.; 1H NMR (DMSO-d6) δ 2.85 (s, 3 H), 3.20-3.55 (m, 8 H), 3.65 (broad s, 2 H), 4.40 (broad t, 2 H) 6.05 (s, 2 H), 6.65 (broad s, 1 H), 7.2, (broad d, 1 H), 7.45 (t, 2 H), 7.55 (d, 1 H), 7.69 (7.55, 1 H), 7.60 (dd, 2 H), 7.70 (broad s, 1 H). MS (m/z) 431 (MH+, 2), 170 (33), 113 (100); Anal. (C22H24ClFN4O2.C4H4O4) C, H, N.

Provenance & Evidence