Reacción #68132

Ecuación de reacción

potassium hydroxide

potassium hydroxide

potassium hydroxide

potassium hydroxide

1,4-dioxane

4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarbonitrile

potassium hydroxide

ethanol

potassium hydroxide

ethanol

→

4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarboxamide

Disolventes

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   Temperaturarefluxed
3. 3
   Temperaturawith heating for 4 hours
4. 4
   Temperaturarefluxed
5. 5
   Temperaturawith heating for 4 hours
6. 6
   Temperaturarefluxed
7. 7
   Temperaturawith heating for 9.5 hours
8. 8
   Temperaturarefluxed
9. 9
   Temperaturawith heating for 1 hour
10. 10
    Temperaturarefluxed
11. 11
    Temperaturawith heating for 8 hours
12. 12
    Temperaturarefluxed
13. 13
    Temperaturawith heating for 6 hours
14. 14
    Otrothe solvent was removed under reduced pressure
15. 15
    workup.ADDITIONwas added
16. 16
    OtroThe organic layer was separated
17. 17
    Extracciónthe aqueous layer was extracted with chloroform
18. 18
    Lavadowashed with aqueous saturated sodium chloride solution
19. 19
    Secadodried over anhydrous magnesium sulfate
20. 20
    Otrothe solvent was removed under reduced pressure
21. 21
    OtroTo the residue thus obtained
22. 22
    Filtraciónthe resulting solid was filtered

Procedimiento

To 1 mL of a 1,4-dioxane solution containing 30 mg of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarbonitrile, 1 mL of 20% aqueous potassium hydroxide solution and 1 mL of ethanol were added at room temperature and refluxed with heating for 4 hours. Further, 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 4 hours, thereafter 1.5 mL of 20% aqueous potassium hydroxide solution was further added and refluxed with heating for 9.5 hours. After 1 mL of 20% aqueous potassium hydroxide solution and 0.5 mL of ethanol were added and refluxed with heating for 1 hour, further 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 8 hours. After 1 mL of 20% aqueous potassium hydroxide solution was added and refluxed with heating for 6 hours, the reaction mixture was cooled to the room temperature, the solvent was removed under reduced pressure. The residue was adjusted to pH 11 with 2.0 mol/L hydrochloric acid and chloroform was added. The organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. To the residue thus obtained, diethyl ether was added, and the resulting solid was filtered to give 21 mg of 4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)-1-(2-(7-methoxy-4-methyl-2-oxoquinolin-1(2H)-yl)ethyl)cyclohexanecarboxamide as a white solid.

Fuente