反応 #43742

反応方程式

5,7-difluoro-1-benzofuran-2-carboxylic acid

(R)-3-aminoquinuclidine dihydrochloride

HATU

N,N-diisopropylethylamine

→

title compound

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]-5,7-difluoro-1-benzofuran-2-carboxamide

溶媒

DMF

反応条件

後処理

1. 1
   その他DMF is removed under reduced pressure
2. 2
   workup.DISSOLUTIONthe crude product is dissolved in 1N aqueous sodium hydroxide solution
3. 3
   抽出The aqueous phase is extracted with ethyl acetate
4. 4
   乾燥The combined organic phases are dried over magnesium sulfate
5. 5
   その他the solvent is removed under reduced pressure
6. 6
   その他a rotary evaporator
7. 7
   洗浄The loaded ion exchanger is washed three times with in each case 30 ml of methanol
8. 8
   洗浄The product is eluted with methanol/triethylamine 95:5
9. 9
   その他The solvent is removed under reduced pressure
10. 10
    その他a rotary evaporator

実験手順

55 mg (0.28 mmol) of 5,7-difluoro-1-benzofuran-2-carboxylic acid, 50 mg (0.25 mmol) of (R)-3-aminoquinuclidine dihydrochloride, 114.6 mg (0.3 mmol) of HATU, 117 mg (0.9 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. 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. 40 mg (52% of theory) of the title compound are isolated.

出典