Reaktion #618297

Reaktionsgleichung

Sodium

Triethylamine

methyl 2-ethyl-5-oxo-6-(piperidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate dihydrochloride

6-cyclopropyl-3-ethoxy-2,4′-difluorobiphenyl-4-carbaldehyde

→

title compound

Ausbeute 62.6%

Methyl 6-(1-((6-cyclopropyl-3-ethoxy-2,4′-difluorobiphenyl-4-yl)methyl)piperidin-4-yl)-2-ethyl-5-oxo-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate

Ausbeute 62.6%

Lösungsmittel

acetic acid

THF

DMA

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe mixture was stirred at room temperature under nitrogen atmosphere for 30 minutes
2. 2
   workup.STIRRINGThe mixture was stirred at the same temperature under nitrogen atmosphere for 60 hours
3. 3
   SonstigeThe mixture was quenched with aqueous saturated sodium hydrogen carbonate solution at room temperature
4. 4
   Extraktionextracted with ethyl acetate
5. 5
   SonstigeThe organic layer was separated
6. 6
   Waschenwashed with water and brine
7. 7
   Trocknendried over anhydrous magnesium sulfate
8. 8
   Einengenconcentrated in vacuo
9. 9
   SonstigeThe residue was purified by a silica gel column chromatography (ethyl acetate/methanol)

Vorschrift

Triethylamine (3.84 g) was added to a suspension of methyl 2-ethyl-5-oxo-6-(piperidin-4-yl)-5,6,7,8-tetrahydro-1,6-naphthyridine-3-carboxylate dihydrochloride (7.41 g) in THF (90 mL) and DMA (30 mL) at room temperature. After being stirred at the same temperature for 30 minutes, 6-cyclopropyl-3-ethoxy-2,4′-difluorobiphenyl-4-carbaldehyde (6.89 g) was added to the reaction mixture. The mixture was stirred at room temperature under nitrogen atmosphere for 30 minutes. Sodium triacetoxyhydroborate (6.04 g) and acetic acid (1.141 g) were added to the reaction mixture at room temperature. The mixture was stirred at the same temperature under nitrogen atmosphere for 60 hours. The mixture was quenched with aqueous saturated sodium hydrogen carbonate solution at room temperature and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by a silica gel column chromatography (ethyl acetate/methanol) to give the title compound (7.17 g).

Quelle