Reaction #2069947

Reaction equation

sodium hydroxide

1-isoquinolinecarbonitrile

hydrochloric acid

4-Bromoanisol

1,2-dibromoethane

magnesium

→

title compound

1-Isoquinolyl(4-methoxyphenyl)ketone

Solvents

tetrahydrofuran

methanol

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturewhile heating
2. 2
   Temperatureunder reflux for 45 minutes
3. 3
   workup.STIRRINGthis reaction mixture was stirred at room temperature for 2 hours
4. 4
   workup.ADDITIONwere added
5. 5
   Temperaturethis mixture was heated
6. 6
   Temperatureunder reflux for 1.5 hours
7. 7
   TemperatureAfter cooling on ice
8. 8
   Extractionextracted with ether
9. 9
   Washwashed with saturated brine
10. 10
    Dryingdried over anhydrous magnesium sulfate
11. 11
    Concentrationconcentrated under reduced pressure
12. 12
    OtherThe residue was purified by silica gel column chromatography

Procedure

4-Bromoanisol (15.3 ml, 122 mmol) and a catalytic amount of 1,2-dibromoethane as an initiator were added to a mixed solution of magnesium (3059 mg, 125.8 mmol) and tetrahydrofuran (20 ml) under nitrogen atmosphere, and this reaction mixture was stirred while heating under reflux for 45 minutes. The mixture was cooled to 0° C., a solution of 1-isoquinolinecarbonitrile (10.78 g, 69.9 mmol) in tetrahydrofuran (30 ml) was added dropwise thereto, and this reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was cooled on ice, concentrated hydrochloric acid (24 ml) and methanol (120 ml) were added, and this mixture was heated under reflux for 1.5 hours. After cooling on ice, the mixture was adjusted to pH 8 by adding aqueous sodium hydroxide, extracted with ether, washed with saturated brine, 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 (15.87 g).

Source