tert-Butoxy bis(dimethylamino)methane → 4-bromo-5-methyl-1H-indole

HRID 25273

반응식

HRID 25273 반응식
[CH3:1]C(OC(N(C)C)N(C)C)(C)C.[CH3:13][C:14]1[C:19]([N+:20]([O-])=O)=[CH:18][CH:17]=[C:16]([CH3:23])[C:15]=1[Br:24]>CN(C=O)C.[Zn]>[Br:24][C:15]1[C:16]([CH3:23])=[CH:17][CH:18]=[C:19]2[C:14]=1[CH:13]=[CH:1][NH:20]2

참가 물질

5

반응물 2

HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 123959052-Bromo-1,3-dimethyl-4-nitrobenzene

생성물 1

HCID 104886354-bromo-5-methyl-1H-indole수율 29%

시약·촉매·용매 2

HCID 23994Zinc촉매HCID 6228Dimethylformamide용매

반응 조건

온도
122.5 °C

실험 절차

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.

후처리

  1. customis mostly consumed
  2. temperatureto cool to room temperature
  3. additionpoured into water (300 ml)
  4. extractionextracted with dichloromethane (100 ml×3)
  5. dry with materialThe combined extracts are dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain
  9. customThis material is carried on to the next step without purification
  10. dissolutionThe crude mixture is dissolved in acetic acid/water (250 ml of 4:1)
  11. temperaturecooled to 0° C.
  12. additionadded slowly in portions
  13. additionAfter complete addition
  14. temperaturethe reaction mixture is heated at 110° C. for 4 h
  15. customZinc is removed by filtration through a celite pad
  16. extractionthe filtrate is extracted with dichloromethane (100 ml×3)
  17. dry with materialThe combined extracts are dried over anhydrous sodium sulfate
  18. concentrationconcentrated
  19. custompurified by flash chromatography on silica
  20. customget (EtOAc/Hexane 1:20)

출처 및 근거

ORD 기록
ord-bf051fea029f4c638754337c8a6df60b
출처 데이터셋
uspto-grants-2005_02
특허 번호
US06858637B2

연결된 노트

불러오는 중…