Lithium Hydroxide → 4-(6-(4-butylphenyl)-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxybenzoic acid

Participants

Reaction Conditions

Reaction Steps

Steps 8 and 9: To a mixture of 4-(6-chloro-3-ethyl-7-fluoro-1H-indol-2-yl)-2-hydroxy-benzoic acid methyl ester (50 mg, 0.14 mmol), 4-n-butyl-phenylboronic acid (50 mg, 0.28 mmol), and cesium fluoride (78 mg, 0.52 mmol) in dioxane (3 mL, anhydrous) is added palladium bis(tri-tert-butyl-phosphine) (6 mg, 10 mol %). This mixture is purged with N2 for 3 minutes and then heated in a sealed tube at 120° C. for 4 hours. The mixture is cooled to room temperature, filtered, and the filtrate is concentrated. The resulting residue is dissolved in ethanol/H2O (1 mL/0.1 mL) and transferred to a microwave tube. LiOH (12 mg, 0.54 mmol) is added and the mixture is heated at 120° C. for 6 minutes under microwave irradiation. The crude product mixture is filtered. After concentration of the filtrate, the crude product is purified by preparative RP LC-MS to give 4-[6-(4-butyl-phenyl)-3-ethyl-7-fluoro-1H-indol-2-yl]-2-hydroxy-benzoic acid as a yellow solid: 1H NMR (400 MHz, CD3OD) δ 7.96 (d, 1H, J=8.8 Hz), 7.50 (d, 2H, J=8 Hz), 7.42 (d, 1H, J=8.4 Hz), 7.24 (d, 2H, J=8 Hz), 7.21-7.20 (m, 2H), 7.10 (dd, 1H, J=8, 8 Hz), 2.95 (q, 2H, J=7.6 Hz), 2.66 (t, 2H, J=8 Hz), 1.65 (m, 2H), 1.40 (m, 2H), 1.34 (t, 3H, J=7.6 Hz), 0.97 (t, 3H, J=7.6 Hz); ESMS m/z 432.2 (M+H+).

Provenance & Evidence