反应详情

To a mixture of 5-cyclopropyl-2-fluoro-4-((trans-4-methylcyclohexyl)-methoxy)benzoic acid (0.255 g, 0.83 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.242 g, 1.26 mmol) and 4-dimethylaminopyridine (0.242 g, 1.98 mmol) in anhydrous dichloromethane (22 mL) was added azetidine-1-sulfonamide (0.173 g, 1.27 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The mixture was poured into 5% aqueous hydrochloric acid (50 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (4×50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by column chromatography (0% to 40% ethyl acetate in hexanes) to afford the title compound (0.114 g, 33%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.66 (d, J=16.7 Hz, 1H), 7.59 (d, J=9.1 Hz, 1H), 6.57 (d, J=14.5 Hz, 1H), 4.25 (t, J=7.7 Hz, 4H), 3.83 (d, J=6.1 Hz, 2H), 2.27 (q, J=7.7 Hz, 1H), 2.11-2.02 (m, 1H), 1.92-1.75 (m, 5H), 1.41-1.29 (m, 1H), 1.25-0.90 (m, 10H), 0.70-0.64 (m, 2H); MS (ES−) m/z 423.26 (M−1).

1. customthe layers were separated
2. extractionThe aqueous layer was extracted with ethyl acetate (4×50 mL)
3. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (0% to 40% ethyl acetate in hexanes)