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-703c145590f64b67b603ff0cb80ce7a6

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08012968B2