Reaction #68130

Reaction equation

4-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)piperidine-4-carbonitrile

(2,3-dihydrobenzo[b](1,4)dioxin-6-yl)acetaldehyde

(2,3-dihydrobenzo[b](1,4)dioxin-6-yl)acetaldehyde

sodium hydrogen carbonate

sodium cyanoborohydride

→

1-(2-(2,3-dihydro-1,4-benzodioxin-6-yl)ethyl)-4-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)piperidine-4-carbonitrile

Yield 80.1%

Solvents

dichloromethane

methanol

dichloromethane

acetic acid

chloroform

water

Conditions

Workup

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   workup.STIRRINGstirred 1 hour and 50 min
3. 3
   workup.ADDITIONwas further added
4. 4
   workup.STIRRINGstirred for 1 hour
5. 5
   Otherthe organic layer was separated
6. 6
   Extractionthe aqueous layer was extracted with chloroform
7. 7
   Washwashed with aqueous saturated sodium chloride solution
8. 8
   Dryingdried over anhydrous magnesium sulfate
9. 9
   Otherthe solvent was removed under reduced pressure
10. 10
    OtherThe residue thus obtained
11. 11
    Otherwas purified by flash silica gel column chromatography[gradient elution of chloroform

Procedure

To 5 mL of methanol solution containing 0.20 g of 4-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)piperidine-4-carbonitrile, 1.5 mL of dichloromethane solution containing 0.33 g of (2,3-dihydrobenzo[b](1,4)dioxin-6-yl)acetaldehyde and 70 μL of acetic acid were added at room temperature, and stirred at the same temperature for 55 min. 77 mg of sodium cyanoborohydride was added at room temperature, and stirred 1 hour and 50 min, thereafter 0.5 mL of dichloromethane solution containing 0.10 g of (2,3-dihydrobenzo[b](1,4)dioxin-6-yl)acetaldehyde was further added and stirred for 1 hour. To the reaction mixture, water, chloroform and aqueous saturated sodium hydrogen carbonate solution were 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, thereafter dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography[gradient elution of chloroform:methanol=99:1-97:3], to give 0.24 g of 1-(2-(2,3-dihydro-1,4-benzodioxin-6-yl)ethyl)-4-(2-(7-methoxy-4-methyl-2-oxo-1,2-dihydroquinolin-1-yl)ethyl)piperidine-4-carbonitrile as a white foam.

Source