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

HRID 25273

反応式

HRID 25273 の反応式
[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

参加物

5

反応物 2

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

生成物 1

HCID 104886354-bromo-5-methyl-1H-indole収率 29%

試薬・触媒・溶媒 2

HCID 23994Zinc触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
122.5 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-bf051fea029f4c638754337c8a6df60b
出典データセット
uspto-grants-2005_02
特許番号
US06858637B2

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