Reaktion #499698

Reaktionsgleichung

ammonium isothiocyanate

benzoyl chloride

7-[1-(pyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline

→

title compound

Ausbeute 44.8%

7-[1-(Pyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carbothioamide

Ausbeute 44.8%

Lösungsmittel

acetone

acetone

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   workup.STIRRINGthe mixture was stirred at the same temperature for 1 hour
4. 4
   SonstigeAfter completion of the reaction
5. 5
   Sonstigethe solvent was evaporated
6. 6
   workup.ADDITIONwater was added
7. 7
   ExtraktionThe mixture was extracted with chloroform
8. 8
   WaschenThe organic layer was washed successively with water and saturated brine
9. 9
   Trocknendried over anhydrous sodium sulfate
10. 10
    Sonstigethe solvent was evaporated
11. 11
    workup.ADDITIONTo the obtained residue was added conc. hydrochloric acid (10 ml)
12. 12
    workup.STIRRINGthe mixture was stirred
13. 13
    Temperaturunder reflux for 1 hour
14. 14
    SonstigeAfter completion of the reaction, water
15. 15
    workup.ADDITIONwas added
16. 16
    Waschenthe mixture was washed successively with ethyl acetate and chloroform
17. 17
    EinengenThe aqueous layer was concentrated
18. 18
    workup.DISSOLUTIONthe resultant residue was dissolved in water
19. 19
    FiltrationThis was filtrated
20. 20
    Einengenthe filtrate was concentrated
21. 21
    SonstigeThe obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:1-20:1)
22. 22
    Sonstigedried under reduced pressure

Vorschrift

To a solution of ammonium isothiocyanate (220 mg) in acetone (4.5 ml) was dropwise added benzoyl chloride (0.32 ml) at room temperature, and the mixture was stirred at 75° C. for 10 min. Then, a mixture of 7-[1-(pyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline (850 mg) in acetone (4.5 ml) and methylene chloride (4.5 ml) was added dropwise, and the mixture was stirred at the same temperature for 1 hour. After completion of the reaction, the solvent was evaporated and water was added. The mixture was extracted with chloroform. The organic layer was washed successively with water and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. To the obtained residue was added conc. hydrochloric acid (10 ml), and the mixture was stirred under reflux for 1 hour. After completion of the reaction, water was added and the mixture was washed successively with ethyl acetate and chloroform. The aqueous layer was concentrated and the resultant residue was dissolved in water and ethanol, and neutralized with ion-exchange resin (IRA-410). This was filtrated and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:1-20:1) and dried under reduced pressure to give the title compound (450 mg).

Quelle