Reaction #76478

Reaction equation

acetic anhydride

5-nitroisoquinoline

dimethylsulfate

→

product

Yield 26.0%

N-(1,2,3,4-tetrahydro-2-methyl-5-isoquinolinyl)-acetamide

Yield 26.0%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was cooled
2. 2
   Concentrationconcentrated
3. 3
   workup.DISSOLUTIONThe residue was dissolved in 1500 mL of methanol
4. 4
   ConcentrationThe reaction mixture was then concentrated
5. 5
   workup.DISSOLUTIONthe residue dissolved in CHCl3 (1000 mL)
6. 6
   Washwashed with aqueous 1N NaOH solution (500 mL)
7. 7
   ExtractionThe aqueous phase was extracted with an additional 3000 mL of chloroform
8. 8
   Dryingthe combined organic extracts were dried (Na2SO4)
9. 9
   Concentrationconcentrated
10. 10
    Otherto give an oil
11. 11
    ConcentrationThe reaction mixture was concentrated
12. 12
    workup.DISSOLUTIONthe residue was dissolved in chloroform
13. 13
    Washwashed with aqueous 1N NaOH solution
14. 14
    DryingThe organic phase was dried (Na2SO4)
15. 15
    Concentrationconcentrated
16. 16
    OtherThe residue was purified by chromatography (10:2 EtOAc:EtOH)
17. 17
    OtherThe purified residue was recrystallized from EtOAc

Procedure

A solution of 5-nitroisoquinoline (200 g, 1.15 mol) in 1000 mL of dimethylformamide was treated with dimethylsulfate (160 g, 1.27 mol), and the resulting solution was heated to 90° C. until no starting material remained. The reaction mixture was cooled and concentrated. The residue was dissolved in 1500 mL of methanol and hydrogenated over PtO2 (1.0 g) at 52 psi for 15.5 hours. The reaction mixture was then concentrated and the residue dissolved in CHCl3 (1000 mL) and washed with aqueous 1N NaOH solution (500 mL). The aqueous phase was extracted with an additional 3000 mL of chloroform, and the combined organic extracts were dried (Na2SO4) and concentrated to give an oil. The oil was treated with acetic anhydride (700 mL) and the resulting solution stirred at room temperature overnight. The reaction mixture was concentrated and the residue was dissolved in chloroform and washed with aqueous 1N NaOH solution. The organic phase was dried (Na2SO4) and concentrated. The residue was purified by chromatography (10:2 EtOAc:EtOH). The purified residue was recrystallized from EtOAc to give the product (60.6 g, 26%) as a white solid, mp=138-139° C.

Source