Citric Acid → 3-[3-(4-Acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenylamino]-benzoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Combine 1-[4-(3-amino-benzyloxy)-2-hydroxy-3-propyl-phenyl]-ethanone (500 mg, 1.67 mmol), 3-bromo-benzoic acid methyl ester (326 mg, 1.52 mmol) and cesium carbonate (693 mg, 2.13 mmol) in toluene (25 mL) and stir. Purge reaction vessel with argon. Add BINAP [rac-2,2′-Bis(diphenyl-phosphino)-1,1′-binaphthyl] (142 mg, 0.228 mmol), and palladium acetate (34 mg, 0.152 mmol). Purge reaction vessel with argon. Heat to 100° C. After 18 hours, cool to ambient temperature. Add 10% aqueous citric acid, and extract with ethyl acetate. Combine the organic layers, dry with sodium sulfate, filter and concentrate to dryness. Purify the resulting residue by flash chromatography eluting with ethyl acetate:hexanes to yield the title compound as a white solid (280 mg, 43%): 1H NMR (DMSO-d6) δ 0.81 (t, 3H), 1.46 (sextet, 2H), 2.57 (m, 5H), 3.82 (s, 3H), 5.23 (s, 2H), 6.71 (d, 1H), 6.95 (d, 1H), 7.01 (d, 1H), 7.19 (m, 1H), 7.28-7.41 (m, 4H), 7.65 (m, 1H), 7.81 (d, 1H), 8.49 (bs, 1H), 12.84 (s, 1H).

Provenance & Evidence