Hydrochloric Acid → N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide

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Reaction Steps

To a 2-dram vial containing tert-butyl 4-{(1R)-1-[(1-benzofuran-2-ylcarbonyl)amino]ethyl}benzoate was added DCM (2.5 mL), and trifluoroacetic acid (0.28 mL, 3.60 mmol). The mixture was stirred at rt for 6 h then evaporated to give an oil residue. To the residue was added HATU (0.10 g, 0.27 mmol), triethylamine (0.25 mL, 1.80 mmol), and DCM (2.5 mL). After stirring at rt for 30 min, O-(tert-butyldimethylsilyl)hydroxylamine (0.053 g, 0.360 mmol) was added. The mixture was stirred at rt for 2 h, then the solvent was completely removed to give a sticky brown oil. To this oil residue was added hydrochloric acid (4.0 mL, 1% v/v in IPA). After stirring at rt for 30 min, the solvent was evaporated to dryness to give a solid. To the solid was then added DMSO (1.1 mL). The solution was filtered and purified by Gilson prep-HPLC [25-50% MeCN—H2O] to give N-((1R)-1-{4-[(hydroxyamino)carbonyl]phenyl}ethyl)-1-benzofuran-2-carboxamide (0.0148 g, 24%) as a white solid. LC-MS: (FA) ES+ 325; 1H NMR (Methanol-d4, 400 MHz) δ 7.71 (m, 3H), 7.60 (d, J=8.5 Hz, 1H), 7.50 (m, 3H), 7.45 (t, J=7.0 Hz, 1H), 7.31 (t, J=7.8 Hz, 1H), 5.30 (q, J=7.2 Hz, 1H), 1.61 (d, J=7.0 Hz, 3H).

Provenance & Evidence