Citric Acid → Ethyl 1-methyl-2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate

2.2 g (10 mmol) of ethyl 2-oxo-1,2-dihydro-1,8-naphthyridine-3-carboxylate was dissolved in a mixed solvent of N,N-dimethylformamide (50 mL) and 1,2-dimethoxyethane (15 mL), and under a nitrogen gas stream, 0.45 g (11 mmol) of 60% sodium hydride (oily) was added thereto at room temperature. The mixture was further stirred for 30 minutes at room temperature. 3.5 g (40 mmol) of lithium bromide was added to the above mixture under ice cooling, and the resulting mixture was stirred for 30 minutes at room temperature. 3.9 g (27.5 mmol) of iodomethane was further added to the mixture at room temperature, and the resulting mixture was stirred for 6 hours at 60° C. The reaction mixture was poured into an aqueous solution of citric acid, and the mixture was extracted with ethyl acetate. The organic phase was washed with brine, an aqueous solution of sodium hydrogen carbonate, and brine in this order, and was dried and concentrated. The residue was washed with diisopropyl ether, and thus 1.66 g (yield: 71%) of the title compound was obtained as a light purple solid.

1. customat room temperature
2. stirringthe resulting mixture was stirred for 30 minutes at room temperature
3. stirringthe resulting mixture was stirred for 6 hours at 60° C
4. extractionthe mixture was extracted with ethyl acetate
5. washThe organic phase was washed with brine
6. dry with materialan aqueous solution of sodium hydrogen carbonate, and brine in this order, and was dried
7. concentrationconcentrated
8. washThe residue was washed with diisopropyl ether

ORD record

ord-05dbc84922be4359871a768d23ec1a8a

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08334236B2