2-(3-Ethoxyphenoxy)-N-[4-hydroxy-2-(isobutylamino)phenyl]acetamide → 2-[(3-Ethoxyphenoxy)methyl]-1-isobutylbenzimidazol-6-ol

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Reaction Steps

A 250 mL flask fitted with a stir-bar and condenser was charged with amine 65b (10.0 g, 27.9 mmol) and AcOH (100 mL). The resultant solution was heated in a 100° C. bath for 1 hr, then concentrated in vacuo to a brown oil. The oil was taken up in EtOAc (200 mL) and washed with saturated NaHCO3 (2×100 mL) and brine (100 mL). Isopropanol (50 mL) and CH2Cl2 (50 mL) were added to break the emulsion. The organic solution was filtered through phase separation paper and concentrated in vacuo to a red-tan solid. The solid was triturated with hexanes:EtOAc 9:1 (50 mL), filtered, pressed with rubber dam, and rinsed with hexanes:EtOAc 9:1 (2×20 mL). The solid was dried to give 8.3 g of 66b as a tan solid (87%). 1H NMR (300 MHz, CDCl3): δ 8.84 (s, 1H), 7.37 (d, 1H), 7.02 (t, 1H), 6.70 (dd, 1H), 6.65 (d, 1H), 6.48 (dd, 1H), 6.44 (t, 1H), 6.37 (dd, 1H), 5.10 (s, 2H), 3.86 (t, 2H), 3.81 (d, 2H), 2.15 (nonet, 1H), 1.23 (t, 3H), 0.78 (d, 6H) ppm. HPLC analysis (0:10:90 H2O:A1:MeOH) showed a purity of 99% with a retention time of 3.5 min.

Provenance & Evidence