反应详情

143 mg (0.55 mmol) of 5-fluoro-7-bromo-1-benzofuran-2-carboxylic acid, 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 according to the general procedure (variant B). DMF is removed under reduced pressure and the crude product is dissolved in 1N aqueous sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate and washed with saturated sodium chloride solution. The combined organic phases are dried over magnesium sulfate and the solvent is removed under reduced pressure using a rotary evaporator. The crude product is taken up in methanol and, together with acidic ion exchange resin (Dowex WX2-200), shaken for about 20 min. The loaded ion exchanger is washed three times with in each case 30 ml of methanol, 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 under reduced pressure using a rotary evaporator. 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 aqueous sodium hydroxide solution
3. extractionThe aqueous phase is extracted with ethyl acetate
4. washwashed with saturated sodium chloride solution
5. dry with materialThe combined organic phases are dried over magnesium sulfate
6. customthe solvent is removed under reduced pressure
7. customa rotary evaporator
8. washThe loaded ion exchanger is washed three times with in each case 30 ml of methanol
9. washThe product is eluted with methanol/triethylamine 95:5
10. customThe solvent is removed under reduced pressure
11. customa rotary evaporator