Reaction #43730

Reaction equation

5-nitrothiophene-2-carboxylic acid

diiso-propylethylamine

TBTU

HOBt

3-aminoquinuclidine dihydrochloride

→

hydrochloride

Yield 48.6%

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

Yield 48.6%

Solvents

DMF

Conditions

Workup

1. 1
   OtherAt RT
2. 2
   ConcentrationFor 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
   OtherThe phases are separated
5. 5
   Extractionthe aqueous phase is repeatedly re-extracted with chloroform
6. 6
   DryingThe combined organic phases are dried over sodium sulfate
7. 7
   Concentrationconcentrated
8. 8
   Otherthe 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
    Concentrationthe mixture is concentrated
11. 11
    Otherthe product is dried under high vacuum

Procedure

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.

Source