Reaktion #729108

Reaktionsgleichung

2-methyl-1,2,3,4-tetrahydroisoquinolin-8-amine

NaOH

NaNO2

HBr

→

8-bromo-2-methyl-1,2,3,4-tetrahydroisoquinoline

Lösungsmittel

HBr H2O

H2O

ethyl acetate

—

petroleum ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeInto a 50 mL 3-necked round bottom flask (named
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   Temperaturwhile cooling to a temperature of 0° C.
4. 4
   workup.STIRRINGthe mixture was stirred for 30 mins at that temperature
5. 5
   SonstigeThen into another 50 mL 3-necked round bottom flask (named B), was purged
6. 6
   Temperaturmaintained with an inert atmosphere of nitrogen
7. 7
   Temperaturwhile cooling to a temperature of 0° C
8. 8
   workup.STIRRINGThe mixture was stirred for 10 minutes
9. 9
   workup.ADDITIONThen was followed by the addition of the reaction solution of flask A with dropwise while the temperature
10. 10
    Temperaturwas maintained at 0° C
11. 11
    Sonstigeto react
12. 12
    workup.STIRRINGwith stirring, for 30 minutes while the temperature
13. 13
    Temperaturwas maintained at 0° C
14. 14
    Sonstigeto react
15. 15
    workup.STIRRINGwith stirring, for an additional 2 hours at room temperature
16. 16
    ExtraktionThe resulting solution was extracted three times with 50 mL of CH2Cl2
17. 17
    Trocknendried over K2CO3
18. 18
    FiltrationA filtration
19. 19
    EinengenThe filtrate was concentrated by evaporation under vacuum
20. 20
    Sonstigea rotary evaporator
21. 21
    SonstigeThe residue was purified
22. 22
    Waschenby eluting through a column with a 1:1 ethyl acetate
23. 23
    SonstigeThis resulted in 0.45 g (65%) of 8-bromo-2-methyl-1,2,3,4-tetrahydroisoquinoline as light yellow oil

Vorschrift

Into a 50 mL 3-necked round bottom flask (named A), was placed 2-methyl-1,2,3,4-tetrahydroisoquinolin-8-amine (500 mg, 3.08 mmol). This was followed by the addition of a solution of HBr (5 mL) in H2O (5 mL), which was added dropwise with stirring, while cooling to a temperature of 0° C. To the above was added NaNO2 (230 mg, 3.33 mmol) in several batches, while cooling to a temperature of 0° C. and the mixture was stirred for 30 mins at that temperature. Then into another 50 mL 3-necked round bottom flask (named B), was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of CuBr (550 mg, 3.83 mmol) in HBr/H2O (3 mol/L) (10 mL), while cooling to a temperature of 0° C. The mixture was stirred for 10 minutes. Then was followed by the addition of the reaction solution of flask A with dropwise while the temperature was maintained at 0° C. The resulting solution was allowed to react, with stirring, for 30 minutes while the temperature was maintained at 0° C. The resulting solution was allowed to react, with stirring, for an additional 2 hours at room temperature. The reaction progress was monitored by TLC(ethyl acetate:petroleum ether=1:1). Adjustment of the pH to 9 was accomplished by the addition of NaOH (10%). The resulting solution was extracted three times with 50 mL of CH2Cl2 and the organic layers combined and dried over K2CO3. A filtration was performed. The filtrate was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluting through a column with a 1:1 ethyl acetate; petroleum ether solvent system. This resulted in 0.45 g (65%) of 8-bromo-2-methyl-1,2,3,4-tetrahydroisoquinoline as light yellow oil.

Quelle