反应详情

143 mg (0.55 mmol) of 5-fluoro-7-bromo-1-benzofuran-2-carboxylic acid (Example 4A), 100 mg (0.50 mmol) of (R)-3-aminoquinuclidine dihydrochloride, 229.14 mg (0.6 mmol) of HATU, 234 mg (1.81 mmol) of N,N-diisopropylethylamine and 2.0 ml of DMF are reacted by general method C. DMF is removed under reduced pressure, and the crude product is dissolved in 1N sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate, and the organic phase is washed with saturated aqueous sodium chloride solution. The combined organic phases are dried over magnesium sulphate, and the solvent is removed in a rotary evaporator under reduced pressure. The crude product is taken up in methanol and shaken together with acidic ion exchanger (Dowex® WX2-200) for about 20 min. The loaded ion exchanger is washed three times with 30 ml of methanol each time, then with water, again with methanol, with dichloromethane and finally again with methanol. The product is eluted with methanol/triethylamine 95:5. The solvent is removed in a rotary evaporator under reduced pressure. 181 mg (98% of theory) of the title compound are isolated.

1. customDMF is removed under reduced pressure
2. dissolutionthe crude product is dissolved in 1N sodium hydroxide solution
3. extractionThe aqueous phase is extracted with ethyl acetate
4. washthe organic phase is washed with saturated aqueous sodium chloride solution
5. dry with materialThe combined organic phases are dried over magnesium sulphate
6. customthe solvent is removed in a rotary evaporator under reduced pressure
7. washThe loaded ion exchanger is washed three times with 30 ml of methanol each time
8. washThe product is eluted with methanol/triethylamine 95:5
9. customThe solvent is removed in a rotary evaporator under reduced pressure