Dimethylformamide → 2-(7-Ethyl-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamido)acetic acid

To a stirred solution of methyl 2-(4-hydroxy-1-methyl-2-oxo-7-(2-(trimethylsilyl)ethynyl)-1,2-dihydroquinoline-3-carboxamido)acetate (0.59 g, 1.5 mmol) in N,N-dimethylformamide (5.0 mL, 1.5 mmol) and methanol (1.0 mL, 1.5 mmol) was added cesium fluoride (0.23 g, 1.5 mmol) under nitrogen. After stirring at room temperature for 1 hour, the mixture was concentrated to remove solvents. The resulting solid was adsorbed onto silica and purified using flash chromatography (15-80% EtOAc:Hex gradient) to afford a yellow solid. The solid was suspended in methanol (10 mL) with Pd/C (20 mol %) and exposed to hydrogen from a balloon for 16 h. The crude reaction mixture was filtered through Celite, and the filter pad was washed with dichloromethane (5'10 mL) under argon. The filtrate was concentrated to give a white solid that was further purified on silica by flash chromatography (100% chloroform). The solid was then treated with 5 N aqueous NaOH (3 mL) in THF (3 mL) for 5 hours. The mixture was acidified to pH 1 using 5 N aqueous HCl, and the resulting precipitate was collected by filtration. After washing the solid with water (5×10 mL) and ether (2×10 ml), the desired material was obtained after drying in a vacuum oven overnight at 50° C. (0.21 g, 38% yield, 3 steps).

1. concentrationthe mixture was concentrated
2. customto remove solvents
3. custompurified
4. customto afford a yellow solid
5. customThe crude reaction mixture
6. filtrationwas filtered through Celite
7. washthe filter pad was washed with dichloromethane (5'10 mL) under argon
8. concentrationThe filtrate was concentrated
9. customto give a white solid
10. customthat was further purified on silica by flash chromatography (100% chloroform)
11. additionThe solid was then treated with 5 N aqueous NaOH (3 mL) in THF (3 mL) for 5 hours
12. filtrationthe resulting precipitate was collected by filtration
13. washAfter washing the solid with water (5×10 mL) and ether (2×10 ml)

ORD record

ord-f981b31105ea472aa208e69d8ccda845

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017626B2