Réaction #70182

Équation de réaction

N,N′-Dimethyl-cyclohexane-1,2-diamine

6-tert-Butyl-3,4-dihydro-2H-isoquinolin-1-one

potassium phosphate tribasic

N,N′-Dimethyl-cyclohexane-1,2-diamine

Acetic acid 2,6-dibromo-benzyl ester

→

title compound

Rendement 6.1%

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

Rendement 6.1%

Solvants

dioxane

Conditions de réaction

Traitement

1. 1
   Températureto reflux for 24 hours
2. 2
   workup.STIRRINGContinued to stir
3. 3
   Températureat reflux for a total of 168 hours
4. 4
   Autreadded ethylacetate (300 mL) and water (100 mL), partitioned
5. 5
   Autreseparated the layers
6. 6
   LavageWashed with further water (2×100 mL)
7. 7
   Lavagefinally washed with brine (1×100 mL)
8. 8
   SéchageThe ethyl acetate layer was dried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated
11. 11
    Autreto give 4.45 g of crude product
12. 12
    AutrePurification on a 240 g Analogix column

Mode opératoire

6-tert-Butyl-3,4-dihydro-2H-isoquinolin-1-one (4 g, 19.67 mmol), Acetic acid 2,6-dibromo-benzyl ester (12.1 g, 2 eq), potassium phosphate tribasic (8.35 g, 2 eq) and copper iodide (787 mg, 0.2 eq) were taken up in dioxane (40 mL). Finally added N,N′-Dimethyl-cyclohexane-1,2-diamine (1.24 mL, 0.4 eq) and the resulting mixture was heated to reflux for 24 hours, after which time more copper iodide (394 mg, 0.1 eq) and N,N′-Dimethyl-cyclohexane-1,2-diamine (0.62 mL, 0.2 eq) were added. Stirred an additional 64 hours and then added more copper iodide (400 mg, 0.1 eq). Continued to stir at reflux for a total of 168 hours. Cooled to room temperature and then added ethylacetate (300 mL) and water (100 mL), partitioned and separated the layers. Washed with further water (2×100 mL) and then finally washed with brine (1×100 mL). The ethyl acetate layer was dried over magnesium sulfate, filtered and concentrated to give 4.45 g of crude product. Purification on a 240 g Analogix column afforded the title compound as a white foamy solid (516 mg) ((M+H)+=431) and recovered 6-tert-Butyl-3,4-dihydro-2H-isoquinolin-1-one (2.188 g).

Source