反应详情

A mixture of 5-fluoro-2-(4-fluorophenoxy)benzoic acid (120 mg, 0.48 mmol), 1-[4-(2H-tetrazol-5-yl)phenyl]methanamine hydrochloride (122 mg, 0.58 mmol), 1-hydroxy-1H-benztriazole monohydrate (110 mg, 0.72 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.72 mmol), and triethylamine (0.27 mL, 1.92 mmol) in dichloromethane (8 mL) and N,N-dimethylforamide (2 mL) was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane (50 mL) and washed with 5% aqueous sodium dihydrogenphosphate solution (30 mL). The organic fraction was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate/acetic acid (30:60:1) to afford 143 mg (73%) of the title compounds as white solids: 1H-NMR (DMSO-d6) δ 8.99 (1H, t, J=5.9 Hz), 7.91 (2H, d, J=8.2 Hz), 7.53–6.99 (8H, m), 4.50 (2H, d, J=5.9 Hz); MS (ESI) m/z 408 (M+H)+, 406 (M−H)−.

1. washwashed with 5% aqueous sodium dihydrogenphosphate solution (30 mL)
2. dry with materialThe organic fraction was dried over magnesium sulfate
3. concentrationconcentrated under reduced pressure
4. customThe residue was purified
5. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate/acetic acid (30:60:1)