Hydrochloric Acid → 3-{5-[3,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-indol-1-ylmethyl]-[1,2,4]oxadiazol-3-yl}-benzoic acid methyl ester

Participants

Reaction Steps

Under an N2 atmosphere combine [3,3-Bis-(4-hydroxy-3,5-dimethyl-phenyl)-2-oxo-2,3-dihydro-indol-1-yl]-acetonitrile (0.501 g, 0.782 mmol), 3-[chloro(hydroxyimino)methyl]-benzoic acid methyl ester (1.17 g, 5.47 mmol), and diethyl ether (20 mL). Add a solution of triethylamine (0.84 mL, 6.02 mmol) in diethyl ether (10 mL) over 30 minutes. Stir the reaction at room temperature overnight. Dilute the reaction with ethyl acetate (200 mL) and water (200 mL). Separate the layers, and dry the organic layer with sodium sulfate. Concentrate in vacuo. Chromatograph on silica gel eluting with 20% ethyl acetate in hexanes and concentrate. Dissolve the resulting compound (0.124 g, 0.152 mmol) in THF (1 mL). Add a solution of tetrabutylammonium fluoride (1.0 M) in THF (0.38 mL) and stir the reaction at room temperature for 30 minutes. Add 1N aqueous HCl(10 mL), ethyl acetate (50 mL), and water (40 mL). Separate the layers and wash the organic layer with brine (50 mL). Dry the ethyl acetate with sodium sulfate, and concentrate in vacuo. Chromatograph on silica gel eluting with a gradient from 25% to 50% ethyl acetate in hexanes to give 0.037 g of the title compound: mass spectrum (ion spray): m/z=590(M+1); 1H NMR(DMSO-d6): δ8.24 (s, 2H), 8.10-8.03 (m, 4H), 7.29-7.25 (m, 2H), 7.17 (d, 1H), 7.09 (t, 1H) 6.71 (s, 1H), 5.48 (s, 2H), 3.87 (s, 3H), 2.04 (s, 12H).

Provenance & Evidence