反応 #43730

反応方程式

5-nitrothiophene-2-carboxylic acid

diiso-propylethylamine

TBTU

HOBt

3-aminoquinuclidine dihydrochloride

→

hydrochloride

収率 48.6%

rac-N-(1-Azabicyclo[2.2.2]oct-3-yl)-5-nitro-1-benzothiophene-2-carboxamide hydrochloride

収率 48.6%

溶媒

DMF

反応条件

後処理

1. 1
   その他At RT
2. 2
   濃縮For work-up, the mixture is concentrated
3. 3
   workup.ADDITIONthe residue is taken up in a mixture of chloroform and excess aqueous sodium hydroxide solution
4. 4
   その他The phases are separated
5. 5
   抽出the aqueous phase is repeatedly re-extracted with chloroform
6. 6
   乾燥The combined organic phases are dried over sodium sulfate
7. 7
   濃縮concentrated
8. 8
   その他the crude product is chromatographed on silica gel (mobile phase: chloroform/methanol/conc. ammonia 100:5:0.5→100:20:2)
9. 9
   workup.ADDITIONexcess HCl in diethyl ether is added
10. 10
    濃縮the mixture is concentrated
11. 11
    その他the product is dried under high vacuum

実験手順

At RT, initially 244 mg (0.76 mmol) of TBTU and 104 mg (0.78 mmol) of HOBt followed by 153 mg (0.77 mmol) of 3-aminoquinuclidine dihydrochloride are added to a solution of 180 mg (0.81 mmol) of 5-nitrothiophene-2-carboxylic acid and diiso-propylethylamine (0.8 ml) in 4 ml of DMF. The mixture is stirred at RT for 4 h. For work-up, the mixture is concentrated and the residue is taken up in a mixture of chloroform and excess aqueous sodium hydroxide solution. The phases are separated and the aqueous phase is repeatedly re-extracted with chloroform. The combined organic phases are dried over sodium sulfate and concentrated, and the crude product is chromatographed on silica gel (mobile phase: chloroform/methanol/conc. ammonia 100:5:0.5→100:20:2). The resulting product is taken up in THF, excess HCl in diethyl ether is added, then the mixture is concentrated and the product is dried under high vacuum. 136 mg (47% of theory) of the hydrochloride are obtained.

出典