Reaction #70178

Reaction equation

6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one

Acetic acid 2,6-dibromo-benzyl ester

potassium carbonate

DMSO

→

Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzyl ester

Yield 27.9%

Solvents

dichoromethane

Conditions

Workup

1. 1
   OtherArgon was bubbled through the mixture for 2 minutes
2. 2
   Otherthe lid was tightly closed
3. 3
   Temperaturethe mixture was heated at 150° C. for an additional 24 hours
4. 4
   Filtrationfiltered through a pad of celite
5. 5
   OtherThe filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide
6. 6
   DryingThe dichloromethane layer was dried over anhydrous magnesium sulfate
7. 7
   Concentrationconcentrated in vacuo
8. 8
   Otherpurified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes)

Procedure

6-Dimethylamino-3,4-dihydro-2H-isoquinolin-1-one (150 mg, 0.789 mmol), Acetic acid 2,6-dibromo-benzyl ester (487 mg, 1.58 mmol), cuprous iodide (30 mg, 0.16 mmol) and potassium carbonate (109 mg, 0.789 mmol) were deposited in a sealed vessel. 3 mL DMSO was added. Argon was bubbled through the mixture for 2 minutes and the lid was tightly closed. This was heated at 150° C. for 24 hours. Cuprous iodide (30 mg, 0.16 mmol) was added and the mixture was heated at 150° C. for an additional 24 hours. This was diluted with dichoromethane and filtered through a pad of celite. The filtrate was partitioned between dichloromethane and 5% aq. ammonium hydroxide. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated in vacuo, and purified by flash chromatography (gradient elution 25 to 50% ethyl acetate/hexanes) to yield Acetic acid 2-bromo-6-(6-dimethylamino-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzyl ester (93 mg, 0.22 mmol). MS (ESI) 417.1 (M+H)+.

Source