Ammonium Chloride → HCID 66962521, compound

1-tert-Butyl 3-ethyl 4-(2,4,5-trifluorophenyl)-5,6-dihydropyridine-1,3(2H)-dicarboxylate (9.98 g) was dissolved in methanol (100 ml), and thereto was added magnesium (6.29 g) under ice-cooling, and the mixture was stirred at room temperature for 2 hours. In an ice-bath, to the reaction mixture was added a saturated aqueous ammonium chloride solution, and the mixture was stirred for 30 minutes. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was dissolved in ethanol (80 ml), and thereto was added sodium ethoxide (20% ethanol solution, 10.62 g) at room temperature, and the mixture was refluxed for 4 hours. The reaction mixture was cooled, and concentrated under reduced pressure. To the residue was added a 5% aqueous sodium hydrogen sulfate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (40 ml) and ethanol (40 ml), and thereto was added 1M aqueous sodium hydroxide solution (41.6 ml) at room temperature, and the mixture was stirred at 60° C. for 3 hours. The mixture was cooled, and the reaction mixture was concentrated under reduced pressure. To the residue was added a 5% aqueous sodium hydrogen sulfate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the title compound (7.89 g).

1. temperaturecooling
2. stirringthe mixture was stirred for 30 minutes
3. extractionThe reaction mixture was extracted with ethyl acetate
4. washthe organic layer was washed with a saturated aqueous sodium chloride solution
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe obtained residue was dissolved in ethanol (80 ml)
9. additionwas added sodium ethoxide (20% ethanol solution, 10.62 g) at room temperature
10. temperaturethe mixture was refluxed for 4 hours
11. temperatureThe reaction mixture was cooled
12. concentrationconcentrated under reduced pressure
13. additionTo the residue was added a 5% aqueous sodium hydrogen sulfate solution
14. extractionthe mixture was extracted with ethyl acetate
15. washThe organic layer was washed with a saturated aqueous sodium chloride solution
16. dry with materialdried over sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. dissolutionThe residue was dissolved in tetrahydrofuran (40 ml)
20. additionethanol (40 ml), and thereto was added 1M aqueous sodium hydroxide solution (41.6 ml) at room temperature
21. stirringthe mixture was stirred at 60° C. for 3 hours
22. temperatureThe mixture was cooled
23. concentrationthe reaction mixture was concentrated under reduced pressure
24. additionTo the residue was added a 5% aqueous sodium hydrogen sulfate solution
25. extractionthe mixture was extracted with ethyl acetate
26. washThe organic layer was washed with a saturated aqueous sodium chloride solution
27. dry with materialdried over sodium sulfate
28. filtrationfiltered
29. concentrationconcentrated under reduced pressure

ORD record

ord-e1d4f6f3bdf648b1aabfff99034bb731

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389511B2