Reaction #684949

Reaction equation

hydrochloric acid

1-Bromo-4-butylbenzene

1,2-dibromoethane

magnesium

tetrahydrofuran

1-isoquinolinecarbonitrile

tetrahydrofuran

→

title compound

(4-Butylphenyl)(1-isoquinolyl)ketone

Solvents

methanol

Conditions

Workup

1. 1
   Temperatureunder reflux for 10 minutes
2. 2
   workup.STIRRINGthis mixture was stirred at room temperature for 1 hour
3. 3
   TemperatureThereafter, the mixture was cooled again to 0° C.
4. 4
   Temperaturethis mixture was heated
5. 5
   Temperatureunder reflux for 2 hours
6. 6
   ConcentrationAfter the mixture was concentrated
7. 7
   workup.DISSOLUTIONthe residue was dissolved in 5 N sodium hydroxide
8. 8
   Filtrationtoluene, and was filtered through celite
9. 9
   OtherThe toluene layer of the filtrate was separated
10. 10
    Washwashed with water
11. 11
    Dryingdried over anhydrous magnesium sulfate
12. 12
    Concentrationconcentrated under reduced pressure
13. 13
    OtherThe residue was purified by silica gel column chromatography

Procedure

1-Bromo-4-butylbenzene (2.29 ml, 13 mmol) and a catalytic amount of 1,2-dibromoethane as an initiator were added to a mixed solution of magnesium (338 mg, 14 mmol) and tetrahydrofuran (6.5 ml) under nitrogen atmosphere, and this mixture was stirred under reflux for 10 minutes. The mixture was cooled to 0° C., a solution of 1-isoquinolinecarbonitrile (1.0 g, 6.5 mmol) in tetrahydrofuran was added, and this mixture was stirred at room temperature for 1 hour, then at 70° C. for 3 hours. Thereafter, the mixture was cooled again to 0° C., concentrated hydrochloric acid (2.6 ml) and methanol (11 ml) were added, and this mixture was heated under reflux for 2 hours. After the mixture was concentrated, the residue was dissolved in 5 N sodium hydroxide and toluene, and was filtered through celite. The toluene layer of the filtrate was separated, washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (1.7 g).

Source