2,2-Dimethyl-1,3-dioxane-4,6-dione → 2-chloro-4-[2-(4-fluorobenzyl)-3-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl]benzonitrile

To a solution of N-(3-chloro-4-cyanophenyl)-4-fluorophenylalanine (3.67 g), Meldrum's acid (1.74 g) and 4-(N,N-dimethylamino)pyridine (2.11 g) in tetrahydrofuran (50 mL) was added N,N′-carbonyldiimidazole (2.24 g, 13.8 mmol) at 0° C., and the mixture was stirred at room temperature overnight. A 5% aqueous potassium hydrogen sulfate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 5% aqueous potassium hydrogen sulfate solution and saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL), and the mixture was refluxed for 45 min. After allowing to room temperature, the organic layer was washed with water and saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was washed with ethyl acetate-isopropyl ether to give the title compound as colorless crystals (yield: 2.54 g, 64%).

1. extractionthe mixture was extracted with ethyl acetate
2. washThe organic layer was washed with 5% aqueous potassium hydrogen sulfate solution and saturated brine
3. dry with materialdried over magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
6. temperaturethe mixture was refluxed for 45 min
7. customAfter allowing to room temperature
8. washthe organic layer was washed with water and saturated brine
9. dry with materialdried over magnesium sulfate
10. customThe solvent was evaporated under reduced pressure
11. washthe obtained residue was washed with ethyl acetate-isopropyl ether

ORD record

ord-a29ade680bae4ddfa3b71a377ceb5bdf

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08420694B2