反応 #76478

反応方程式

acetic anhydride

5-nitroisoquinoline

dimethylsulfate

→

product

収率 26.0%

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

収率 26.0%

溶媒

dimethylformamide

反応条件

後処理

1. 1
   温度The reaction mixture was cooled
2. 2
   濃縮concentrated
3. 3
   workup.DISSOLUTIONThe residue was dissolved in 1500 mL of methanol
4. 4
   濃縮The reaction mixture was then concentrated
5. 5
   workup.DISSOLUTIONthe residue dissolved in CHCl3 (1000 mL)
6. 6
   洗浄washed with aqueous 1N NaOH solution (500 mL)
7. 7
   抽出The aqueous phase was extracted with an additional 3000 mL of chloroform
8. 8
   乾燥the combined organic extracts were dried (Na2SO4)
9. 9
   濃縮concentrated
10. 10
    その他to give an oil
11. 11
    濃縮The reaction mixture was concentrated
12. 12
    workup.DISSOLUTIONthe residue was dissolved in chloroform
13. 13
    洗浄washed with aqueous 1N NaOH solution
14. 14
    乾燥The organic phase was dried (Na2SO4)
15. 15
    濃縮concentrated
16. 16
    その他The residue was purified by chromatography (10:2 EtOAc:EtOH)
17. 17
    その他The purified residue was recrystallized from EtOAc

実験手順

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.

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