3-Buten-2-one, 4-methoxy- → 1-(4-Fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid

To a 4-necked 3 L round bottom flask, is added EtOH (1500 mL), ethyl 3-(4-fluorophenylamino)-3-oxopropanoate (139 g, 617 mmol), sodium ethoxide (65.6 g, 925 mmol) and 4-methoxy-3-buten-2-one (103 g, 925 mmol). The mixture is refluxed for 3 hours. After the solution is cooled to RT, the reaction mixture is concentrated under reduced pressure to remove the EtOH. The residue is diluted with DCM (700 mL) and 1 M HCl (1500 mL). The aqueous phase is extracted with DCM (3×500 mL). The combined organic extracts are washed with saturated aqueous sodium chloride (1000 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue is triturated with EtOAc (150 mL) at RT (10-15° C.) for 1 hour. After filtration and washing with EtOAc (50 mL), 1-(4-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxylic acid is obtained as a yellow solid (85.3 g, 56% yield). MS (m/z): 248 (M+H).

1. temperatureThe mixture is refluxed for 3 hours
2. concentrationthe reaction mixture is concentrated under reduced pressure
3. customto remove the EtOH
4. additionThe residue is diluted with DCM (700 mL) and 1 M HCl (1500 mL)
5. extractionThe aqueous phase is extracted with DCM (3×500 mL)
6. washThe combined organic extracts are washed with saturated aqueous sodium chloride (1000 mL)
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated under reduced pressure
9. customThe residue is triturated with EtOAc (150 mL) at RT (10-15° C.) for 1 hour
10. filtrationAfter filtration
11. washwashing with EtOAc (50 mL)

ORD record

ord-489bd0b1618d4754ae3f655517d9fb5d

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030302B2