Hydrochloric Acid → 4-[2-(5-Cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid

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Reaction Steps

A flask is charged with 4-[2-(5-cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid methyl ester (Example 61, 0.150 g, 0.36 mmol) in MeOH (5 mL). Aqueous lithium hydroxide (1 M, 0.912 mL, 0.912 mmol) is added and the mixture is refluxed overnight. The reaction mixture is then acidified to pH 1 using 1 M aqueous HCl solution and the methanol is removed in vacuo. The resulting solution is extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 9:1) to afford 4-[2-(5-cyano-3-methyl-2-pyridin-3-yl-indol-1-yl)-ethoxy]-benzoic acid as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 2.27 (s, 3H), 4.22 (t, J=5.1 Hz, 2H), 4.60 (t, J=5.2 Hz, 2H), 6.72 (d, J=8.8 Hz, 2H), 7.57 (dd, J=8.6, 1.5 Hz, 1H), 7.62-7.72 (m, 1H), 7.76 (d, J=8.6 Hz, 1H), 7.86 (d, J=8.6 Hz, 2H), 8.02 (d, J=7.8 Hz, 1H), 8.07 (s, 1H), 8.72 (br. s., 2H). HRMS (ESI) m/z 398.1487 [(M+H)+ Calcd for C24H20N3O3: 398.1505].

Provenance & Evidence