Reacción #472843

Ecuación de reacción

sodium hydrogen carbonate

sodium triacetoxyborohydride

(2-methoxy-7-oxopyrido(2,3-d)pyrimidin-8(7H)-yl)acetaldehyde

tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate

→

tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(2-methoxy-7-oxopyrido(2,3-d)pyrimidin-8(7H)-yl)ethyl)piperidin-4-yl)carbamate

Rendimiento 66.1%

Disolventes

Chloroform

dichloromethane

dichloromethane

acetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture was stirred for 2 hours 30 minutes
2. 2
   OtroAfter leaving overnight
3. 3
   workup.STIRRINGthe mixture was stirred at room temperature for 4 hours
4. 4
   Otrothe organic layer was separated
5. 5
   Extracciónthe aqueous layer was extracted with chloroform
6. 6
   Lavadothe resultant solution was washed with a saturated aqueous sodium chloride solution
7. 7
   Secadodried over anhydrous magnesium sulfate
8. 8
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
9. 9
   OtroThe resultant residue was purified by silica gel column chromatography
10. 10
    Lavadoelution with chloroform

Procedimiento

To a solution of 0.33 g of (2-methoxy-7-oxopyrido(2,3-d)pyrimidin-8(7H)-yl)acetaldehyde in 15 mL of dichloromethane, a solution of 0.53 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(piperidin-4-yl)carbamate in 5.3 mL of dichloromethane, and 87 μL of acetic acid were added, and the mixture was stirred at room temperature for 1 hour 30 minutes. To the reaction mixture, 0.40 g of sodium triacetoxyborohydride was added, and the mixture was stirred for 2 hours 30 minutes. After leaving overnight, the mixture was stirred at room temperature for 4 hours. Chloroform and a saturated aqueous sodium hydrogen carbonate solution were added to the reaction mixture, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using gradient elution with chloroform:methanol=50:1 to 10:1 to obtain 0.55 g of tert-butyl (2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)(1-(2-(2-methoxy-7-oxopyrido(2,3-d)pyrimidin-8(7H)-yl)ethyl)piperidin-4-yl)carbamate as a light yellow foam.

Fuente