Reaction #1027

Reaction equation

Methyl magnesium chloride

isoquinoline-3-carbonitrile

THF

→

3-acetyl-isoquinoline

Yield 14.0%

Conditions

Workup

1. 1
   workup.ADDITIONAfter the addition the reaction mixture
2. 2
   Otherquenched with water
3. 3
   workup.ADDITIONHydrochloric acid (2M aqueous solution) was added to the reaction mixture until the aqueous phase
4. 4
   workup.STIRRINGAfter stirring for 30 minutes the
5. 5
   Extractionextracted with ether (×2)
6. 6
   WashThe combined extracts were washed with water
7. 7
   Otherdried
8. 8
   Concentrationconcentrated
9. 9
   Otherto give a crystalline solid
10. 10
    OtherRecrystalisation from hexane

Procedure

Methyl magnesium chloride (2.6 ml of a 3.0M solution in THF) was added dropwise to a solution of isoquinoline-3-carbonitrile at 0°-5° C. After the addition the reaction mixture was stirred at room temperature for 1 hour, then quenched with water. Hydrochloric acid (2M aqueous solution) was added to the reaction mixture until the aqueous phase was pH2. After stirring for 30 minutes the aqueous was neutralised with sodium bicarbonate (solid) and extracted with ether (×2). The combined extracts were washed with water, dried and concentrated to give a crystalline solid. Recrystalisation from hexane gave 3-acetyl-isoquinoline (0.55 g, 14% yield) as a pale yellow solid m.p. 84.4°-86.8° C. 1H NMR: 2.83(3H,s); 7.69-7.81(2H,m); 7.99(1H,m); 8.04(1H,m); 8.49(1H,m); 9.29(1H,s) ppm.

Source