Reaktion #68094

Reaktionsgleichung

sodium hydrogen carbonate

sodium cyanoborohydride

sodium cyanoborohydride

N-cyclopropyl-7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinoline-4-carboxamide

tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate

→

tert-butyl (1-(2-(4-((cyclopropylamino)carbonyl)-7-methoxy-2-oxoquinolin-1-(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)carbamate

Ausbeute 47.5%

Lösungsmittel

chloroform

methanol

acetic acid

methanol

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added at room temperature
2. 2
   workup.STIRRINGstirred at the same temperature for 2 hours
3. 3
   workup.STIRRINGstirred at the same temperature for 2 hours and 15 min
4. 4
   workup.STIRRINGstirred at the same temperature for 2 hours
5. 5
   Temperaturcooling
6. 6
   workup.ADDITIONwere added
7. 7
   Sonstigethe organic layer was separated
8. 8
   Extraktionthe aqueous layer was extracted with chloroform
9. 9
   Waschenwashed with aqueous saturated sodium chloride solution
10. 10
    Trocknendried over anhydrous magnesium sulfate
11. 11
    Sonstigethe solvent was removed under reduced pressure
12. 12
    SonstigeThe residue thus obtained
13. 13
    Sonstigewas purified by flash silica gel column chromatography [gradient elution of chloroform:methanol=100:0-70:30]

Vorschrift

To 1.0 mL of methanol solution containing 0.13 g of N-cyclopropyl-7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinoline-4-carboxamide, 0.16 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate and 25 μL of acetic acid were added at room temperature and stirred at the same temperature for 1.5 hours. To the reaction mixture, 42 mg of sodium cyanoborohydride was added and stirred at the same temperature for 2 hours. Further, 42 mg of sodium cyanoborohydride was added and stirred at the same temperature for 2 hours and 15 min. 76 μL of acetic acid was added and stirred at the same temperature for 2 hours. To the mixture, aqueous saturated sodium hydrogen carbonate solution was added under ice-cooling to be adjusted to pH 8.7, 5.0 mL of methanol and 15 mL of chloroform 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, 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=100:0-70:30], to give 0.13 g of tert-butyl (1-(2-(4-((cyclopropylamino)carbonyl)-7-methoxy-2-oxoquinolin-1-(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)carbamate as a white foam.

Quelle