3-Buten-2-one, 4-methoxy- → 6-Methyl-2-oxo-1-phenyl-1,2-dihydro-pyridine-3-carboxylic acid

Ethyl 3-oxo-3-(phenylamino)propionate (56.8 g, 0.27 mol) and 4-methoxy-3-buten-2-one (30.2 g, 0.30 mol) were dissolved in methanol (300 mL), and 20% sodium ethoxide. (112 g, 0.33 mol) was added dropwise thereto at room temperature. After the dropwise addition, the mixture was refluxed for 8 hours under heating. The reaction mixture was cooled and then concentrated under reduced pressure, and thus obtained residue was dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL). To the resultant solution, lithium hydroxide monohydrate (23.0 g, 0.55 mol) was added, and the mixture was stirred overnight at room temperature. The reaction mixture was poured into water, and washed with ethyl acetate. The aqueous layer was acidified by adding citric acid, and then extracted with chloroform. The organic layer was washed with water, dried, and concentrated, and thus obtained crystal was washed with ethyl acetate, to obtain 43.4 g of a desired product (yield: 69%).

1. addition(112 g, 0.33 mol) was added dropwise
2. customat room temperature
3. additionAfter the dropwise addition
4. temperaturethe mixture was refluxed for 8 hours
5. temperatureunder heating
6. temperatureThe reaction mixture was cooled
7. concentrationconcentrated under reduced pressure, and thus obtained residue
8. dissolutionwas dissolved in a mixed solution of 1,4-dioxane (200 mL) and water (200 mL)
9. washwashed with ethyl acetate
10. additionby adding citric acid
11. extractionextracted with chloroform
12. washThe organic layer was washed with water
13. customdried
14. concentrationconcentrated
15. washthus obtained crystal was washed with ethyl acetate

ORD record

ord-b3c9bfd272134a5d88170c6def6d32da

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076487B2