反应详情

温度

0 °C

To a stirred solution of methyl 3-(((2-fluorophenyl)amino)methyl)benzoate (0.3 g, 1.157 mmol) in anhydrous pyridine (6 mL) at 0° C. under N2 was added 4-(dimethylamino)pyridine (0.014 g, 0.116 mmol) followed by (R)-quinuclidin-3-yl carbonochloridate hydrochloride (0.314 g, 1.39 mmol) in one portion. After stirring at 0° C. for 1 hour the reaction was allowed to warm to room temperature. After 2.5 hours, further (R)-quinuclidin-3-yl carbonochloridate (0.628 g, 2.777 mmol) was added, and the reaction was stirred at room temperature for 65 hours. The reaction was quenched by addition of 10% aqueous potassium carbonate solution and extracted with ethyl acetate (×3). The combined organic extracts were washed with brine and dried (sodium sulfate), filtered and the solvent was removed in vacuo to afford a brown oil. The crude material was purified by silica gel column chromatography eluting sequentially with ethyl acetate, 5% methanol in ethyl acetate, 5% 7N methanolic ammonia in ethyl acetate and 10% 7N methanolic ammonia in ethyl acetate to afford the title compound as a yellow oil (0.349 g, 73%).

1. temperatureto warm to room temperature
2. waitAfter 2.5 hours
3. stirringthe reaction was stirred at room temperature for 65 hours
4. customThe reaction was quenched by addition of 10% aqueous potassium carbonate solution
5. extractionextracted with ethyl acetate (×3)
6. washThe combined organic extracts were washed with brine
7. dry with materialdried (sodium sulfate)
8. filtrationfiltered
9. customthe solvent was removed in vacuo
10. customto afford a brown oil
11. customThe crude material was purified by silica gel column chromatography
12. washeluting sequentially with ethyl acetate, 5% methanol in ethyl acetate, 5% 7N methanolic ammonia in ethyl acetate