反应详情

To a stirred solution of 4-(6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation 1; 1.32 g; 3.52 mmol), 1-hydroxybenzotriazole hydrate (0.59 g; 3.85 mmol) and 2-(2-bromo-4-chlorophenyl)ethanamine (Preparation 5; 0.904 g; 3.85 mmol) in dry dimethylformamide (10 mL) was added 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.806 g; 4.02 mmol) at ambient temperature. After stirring at ambient temperature for 5 hours, the solution was diluted with 100 mL of water, stirred for 10 minutes longer and then extracted with ethyl acetate (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (Biotage 40M), eluting with hexane and ethyl acetate to provide ethyl 7-(4-(2-bromo-4-chlorophenethylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate as a white solid (1.21 g). MS (apci, pos) m/z=594.

1. stirringstirred for 10 minutes longer
2. extractionextracted with ethyl acetate (3×15 mL)
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by silica gel chromatography (Biotage 40M)
7. washeluting with hexane and ethyl acetate