Реакция #809355

Уравнение реакции

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

Растворители

dichloromethane

ethyl acetate

DMF

Условия реакции

Обработка

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

Методика

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.

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