Methanol → 3-chloro-5-fluoro-6-methoxy-6,7-dihydro-1,7-naphthyridin-8(5H)-one

Temperature

47.5 °C

A pressure bottle was charged with 3-chloro-1,7-naphthyridin-8(7H)-one (Anichem, 15 g, 83 mmol), MeOH (34 ml), acetonitrile (173 ml) and 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium tetrafluoroborate (Aldrich, 30.9 g, 87 mmol). The mixture was heated to 45-50° C. After 6 hs additional 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium tetrafluoroborate (2.5 g) was added and heating was continued overnight. Water and EtOAc were added to the cooled reaction mixture and the layers were separated. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4. The filtrate was concentrated under reduced pressure a the residue was triturated with EtOAc. The solid was filtered off and the title compound (15.34 g, 66.5 mmol, 80% yield) was isolated as a white solid. MS m/z=231 [M+H]+. Calculated for C9H8ClFN2O2: 230.0

1. temperatureheating
2. customthe layers were separated
3. extractionThe aqueous layer was extracted with EtOAc
4. dry with materialthe combined organic layers were dried over MgSO4
5. concentrationThe filtrate was concentrated under reduced pressure a the residue
6. customwas triturated with EtOAc
7. filtrationThe solid was filtered off

ORD record

ord-f54a32a335d0481d81fb1878bf1bf5f7

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296734B2