Réaction #809355

Équation de réaction

1-azabicyclo[2.2.2]oct-3-ylacetic acid hydrochloride

sodium bicarbonate

pentafluorophenol

EDC

3-bromoaniline

→

title compound

2-(1-Azabicyclo[2.2.2]oct-3-yl)-N-(3-bromophenyl)acetamide Hydrochloride

Solvants

dichloromethane

ethyl acetate

DMF

Conditions de réaction

Traitement

1. 1
   ConcentrationThe residue after concentration in vacuo
2. 2
   workup.WAITleft
3. 3
   workup.STIRRINGto stir at room temperature for a further night
4. 4
   FiltrationAfter the resulting precipitate has been filtered off with suction
5. 5
   Lavagewashed with ethyl acetate
6. 6
   Autrethe two-phase filtrate is separated
7. 7
   Extractionthe aqueous phase is extracted three times with ethyl acetate
8. 8
   SéchageThe combined organic phases are dried over sodium sulfate
9. 9
   Concentrationconcentrated
10. 10
    AutreThe crude mixture is purified by preparative HPLC
11. 11
    ConcentrationThe product fractions are concentrated
12. 12
    workup.ADDITIONtaken up in a 5:1 mixture of methanol and 1M hydrochloric acid
13. 13
    Concentrationagain concentrated
14. 14
    AutreDrying under high vacuum

Mode opératoire

500 mg (2.34 mmol) of 1-azabicyclo[2.2.2]oct-3-ylacetic acid hydrochloride are suspended in 10 ml of dichloromethane and cooled to 0° C. 1.79 g (9.72 mmol) of pentafluorophenol and 699.0 mg (3.65 mmol) of EDC are added, and the mixture is stirred at room temperature overnight. The residue after concentration in vacuo is mixed with 8 ml of DMF and 627.3 mg (3.56 mmol) of 3-bromoaniline and left to stir at room temperature for a further night. The reaction mixture is stirred with 10 ml of 10% strength aqueous sodium bicarbonate solution and 10 ml of ethyl acetate. After the resulting precipitate has been filtered off with suction and washed with ethyl acetate, the two-phase filtrate is separated and the aqueous phase is extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated. The crude mixture is purified by preparative HPLC. The product fractions are concentrated, taken up in a 5:1 mixture of methanol and 1M hydrochloric acid and again concentrated. Drying under high vacuum results in 600 mg (57.3% of theory) of the title compound, which is employed without further purification in the following stages.

Source