Reacción #68130

Ecuación de reacción

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

Rendimiento 80.1%

Disolventes

dichloromethane

methanol

dichloromethane

acetic acid

chloroform

water

Condiciones de reacción

Tratamiento posterior

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
   Otrothe organic layer was separated
6. 6
   Extracciónthe aqueous layer was extracted with chloroform
7. 7
   Lavadowashed with aqueous saturated sodium chloride solution
8. 8
   Secadodried over anhydrous magnesium sulfate
9. 9
   Otrothe solvent was removed under reduced pressure
10. 10
    OtroThe residue thus obtained
11. 11
    Otrowas purified by flash silica gel column chromatography[gradient elution of chloroform

Procedimiento

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.

Fuente