Sodium hydride → 2-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acid

Beteiligte Stoffe

Reaktionsschritte

Sodium hydride (155 mg of a 95% dispersion in mineral oil, 6.13 mmol) was added in portions during 5 min to a stirred and cooled solution (ice-water bath) of 7 (1.0 g, 2.79 mmol) in THF (7 mL). When the evolution of hydrogen subsided DMF (2 mL) was added followed by a solution of bromomethylacrylic acid (505 mg, 3.06 mmol) in THF (1.5 mL). Stirring was continued with cooling (10 min) and then at 22° C. for 30 min. The mixture was concentrated and the residue partitioned between ethyl acetate and water. The organic layer was washed (water, brine), dried (sodium sulfate) and concentrated. The residue was chromatographed on silicic acid (15 g) using the flash technique and eluting with methylene chloride:ethyl acetate:acetic acid (10:1:0.005). The product containing fraction was concentrated on a rotary evaporator to leave 2-((3-cyclohexyl-6-(methoxycarbonyl)-2-(2-vinylphenyl)-1H-indol-1-yl)methyl)acrylic acid (568 mg, 40%) as a yellow gum. A sample (142 mg) was further purified on a Shimadzu preparatory liquid chromatograph. The fraction containing the product was concentrated to leave 13 (R=H) as a granular solid. ESI-MS m/z 433 (MH+), 1H NMR (500 MHz, CHLOROFORM-D) δ ppm 1.07–1.37 (m, 3 H) 1.58–1.88 (m, 7 H) 2.41–2.53 (m, 1 H) 3.93 (s, 3 H) 4.50 (d, J=18.31 Hz, 1 H) 4.84 (d, J=18.31 Hz, 1 H) 4.89 (s, 1 H) 5.13 (d, J=10.99 Hz, 1 H) 5.29 (s, 1 H) 5.68 (d, J=17.70 Hz, 1 H) 6.19 (s, 1 H) 6.36 (dd, J=17.55, 11.14 Hz, 1 H) 7.15 (d, J=7.63 Hz, 1 H) 7.31 (t, J=7.48 Hz, 1 H) 7.45 (t, J=7.63 Hz, 1 H) 7.70 (d, J=7.93 Hz, 1 H) 7.76–7.87 (m, 2 H) 7.96 (s, 1 H).

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