Реакция #48018

Уравнение реакции

ethyl ether

sodium hydride

ethyl 5-t-butyl-1H-indole-2-carboxylate

sodium hydride

4-bromomethylpyridine hydrobromide

4-bromomethylpyridine hydrobromide

→

expected product

Выход 51.0%

Ethyl 5-t-butyl-1-[(pyrid-4-yl)methyl]-1H-indole-2-carboxylate

Выход 51.0%

Растворители

dimethylformamide

dimethylformamide

Условия реакции

Обработка

1. 1
   workup.STIRRINGThe mixture is stirred for 30 minutes at 0° C.
2. 2
   ТемператураThe reaction mixture is cooled
3. 3
   workup.STIRRINGThe mixture is stirred for 30 minutes at 0° C.
4. 4
   workup.WAITfor 30 minutes at 20° C
5. 5
   ТемператураThe reaction mixture is cooled again to 0° C.
6. 6
   workup.WAITAfter 30 minutes at 0° C.
7. 7
   workup.STIRRINGThe reaction mixture is then stirred for 20 hours at 20° C
8. 8
   ДругоеThe organic phase is separated out
9. 9
   Экстракцияthe aqueous phase is re-extracted with 50 ml of ethyl ether
10. 10
    Промывкаwashed with 50 ml of water
11. 11
    Сушкаdried over sodium sulfate
12. 12
    Фильтрацияfiltered
13. 13
    Концентрированиеconcentrated under reduced pressure
14. 14
    ДругоеThe residue is purified by preparative chromatography (eluent: dichloromethane/acetone)

Методика

A solution of 1 g (4.08 mmol) of ethyl 5-t-butyl-1H-indole-2-carboxylate is added dropwise to a suspension of 0.33 g (8.15 mmol) of 60% sodium hydride in 10 ml of dimethylformamide, stirred at 0° C. under argon. The mixture is stirred for 30 minutes at 0° C. and then for 30 minutes at 20° C. The reaction mixture is cooled and 1.06 g (4.08 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The mixture is stirred for 30 minutes at 0° C. and then for 30 minutes at 20° C. The reaction mixture is cooled again to 0° C. and a further 0.33 g (8.15 mmol) of 60% sodium hydride in 10 ml of dimethylformamide is added. After 30 minutes at 0° C., 1.06 g (4.08 mmol) of 4-bromomethylpyridine hydrobromide are added portionwise. The reaction mixture is then stirred for 20 hours at 20° C. After this time, the mixture is poured into a solution of 100 ml of ice-water and 70 ml of ethyl ether. The organic phase is separated out and the aqueous phase is re-extracted with 50 ml of ethyl ether. The organic phases are combined, washed with 50 ml of water and then dried over sodium sulfate, filtered and then concentrated under reduced pressure. The residue is purified by preparative chromatography (eluent: dichloromethane/acetone). 0.7 g of expected product is obtained in the form of an oil, which is used without further purification in the subsequent synthesis.

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