Reaktion #8187

Reaktionsgleichung

4-bromobenzamide

bis(pinacolato)diboron

potassium acetate

trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

sodium carbonate

→

{2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester

Ausbeute 58.5%

Lösungsmittel

dimethylsulfoxide

brine

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture is heated to 80° C. overnight
2. 2
   WaschenThe organic fraction is washed seven times with brine
3. 3
   Trocknendried over anhydrous sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Sonstigeevaporated
6. 6
   SonstigeThe residue is purified
7. 7
   Waschensilica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution)

Vorschrift

A solution of 4-bromobenzamide (150 mg, 0.75 mmol), bis(pinacolato)diboron (209 mg, 0.825 mmol), potassium acetate (0.221 g, 2.25 mmol) and {1,1′-bis(diphenylphosphino)-ferrocene}dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) in dimethylsulfoxide (5 mL) is heated to 80° C. for two hours. The mixture is cooled to 20° C. and trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (262 mg, 0.600 mmol), {1,1′-bis(diphenylphosphino)-ferrocene}dichloropalladium dichloromethane complex (18 mg, 0.0225 mmol) and sodium carbonate (1.9 mL, 2M, 3.75 mmol) are added. The mixture is heated to 80° C. overnight. The mixture is diluted with brine and ethyl acetate. The organic fraction is washed seven times with brine, then dried over anhydrous sodium sulfate, filtered and evaporated. The residue is purified using silica gel chromatography (dichloromethane/10% methanol, 0.7M ammonia in dichloromethane gradient elution) to give 143 mg of {2-[7-(4-carbamoyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester (58%). FDMS m/e=408 (M++1).

Quelle