Reaction #68133

Reaction equation

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

→

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 3 hours
8. 8
   Otherthe solvent was removed under reduced pressure
9. 9
   workup.ADDITIONwas added
10. 10
    OtherThe organic layer was separated
11. 11
    Washwashed with aqueous saturated sodium chloride solution
12. 12
    Dryingdried over anhydrous magnesium sulfate
13. 13
    Otherthe solvent was removed under reduced pressure
14. 14
    OtherTo the residue thus obtained
15. 15
    Filtrationthe resulting solid was filtered

Procedure

To 1.5 mL of a 1,4-dioxane solution containing 90 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, 2 mL of the solution was added and for 9.5 hours, 1 mL of the solution was added and for 1 hour, 1 mL of the solution was added and for 8 hours, further 1 mL of the solution was added and refluxed with heating for 3 hours. The reaction mixture was cooled to the room temperature, and the solvent was removed under reduced pressure. The residue was adjusted to pH 11 with 2.0 mol/L hydrochloric acid and ethyl acetate was added. The organic layer was separated, and 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 53 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