Reaction #68132

Reaction equation

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

Solvents

diethyl ether

Conditions

Workup

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   Temperaturerefluxed
3. 3
   Temperaturewith heating for 4 hours
4. 4
   Temperaturerefluxed
5. 5
   Temperaturewith heating for 4 hours
6. 6
   Temperaturerefluxed
7. 7
   Temperaturewith heating for 9.5 hours
8. 8
   Temperaturerefluxed
9. 9
   Temperaturewith heating for 1 hour
10. 10
    Temperaturerefluxed
11. 11
    Temperaturewith heating for 8 hours
12. 12
    Temperaturerefluxed
13. 13
    Temperaturewith heating for 6 hours
14. 14
    Otherthe solvent was removed under reduced pressure
15. 15
    workup.ADDITIONwas added
16. 16
    OtherThe organic layer was separated
17. 17
    Extractionthe aqueous layer was extracted with chloroform
18. 18
    Washwashed with aqueous saturated sodium chloride solution
19. 19
    Dryingdried over anhydrous magnesium sulfate
20. 20
    Otherthe solvent was removed under reduced pressure
21. 21
    OtherTo the residue thus obtained
22. 22
    Filtrationthe resulting solid was filtered

Procedure

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.

Source