Reaktion #53551

Reaktionsgleichung

Bredereck's reagent

2,6-dimethyl-3-nitrobromobenzene

→

4-bromo-5-methylindole

Ausbeute 29.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeis mostly consumed
2. 2
   Temperaturto cool to room temperature
3. 3
   workup.ADDITIONpoured into water (300 ml)
4. 4
   Extraktionextracted with dichloromethane (100 ml×3)
5. 5
   TrocknenThe combined extracts are dried over anhydrous sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   Sonstigeto obtain
9. 9
   SonstigeThis material is carried on to the next step without purification
10. 10
    workup.DISSOLUTIONThe crude mixture is dissolved in acetic acid/water (250 ml of 4:1)
11. 11
    Temperaturcooled to 0° C.
12. 12
    workup.ADDITIONadded slowly in portions
13. 13
    workup.ADDITIONAfter complete addition
14. 14
    Temperaturthe reaction mixture is heated at 110° C. for 4 h
15. 15
    SonstigeZinc is removed by filtration through a celite pad
16. 16
    Extraktionthe filtrate is extracted with dichloromethane (100 ml×3)
17. 17
    TrocknenThe combined extracts are dried over anhydrous sodium sulfate
18. 18
    Einengenconcentrated
19. 19
    Sonstigepurified by flash chromatography on silica
20. 20
    Sonstigeget (EtOAc/Hexane 1:20)

Vorschrift

Bredereck's reagent (tert-butoxybis(dimethylamino)methane—16 g, 91 mmol) is added at room temperature to a solution of 2,6-dimethyl-3-nitrobromobenzene (20 g, 87 mmol) in anhydrous DMF (120 ml). The reaction mixture is heated at 120-125° C. under N2 for 5 hours or until starting material is mostly consumed according to TLC. The reaction mixture is allowed to cool to room temperature, poured into water (300 ml), and extracted with dichloromethane (100 ml×3). The combined extracts are dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a mixture of enamines as a dark brown oil. This material is carried on to the next step without purification. The crude mixture is dissolved in acetic acid/water (250 ml of 4:1), cooled to 0° C. and treated with zinc dust (57 g, 870 mmol) added slowly in portions. After complete addition, the reaction mixture is heated at 110° C. for 4 h. Zinc is removed by filtration through a celite pad and the filtrate is extracted with dichloromethane (100 ml×3). The combined extracts are dried over anhydrous sodium sulfate, concentrated and purified by flash chromatography on silica get (EtOAc/Hexane 1:20) to obtain 4-bromo-5-methylindole (5.3 g) (21) as a light purple oil.

Quelle