Pyridine → HCID 67890755, compound

Anhydrous dichloromethane (50 ml), 3-(ethyl(phenyl)amino)-3-oxo-propanoic acid (IV) (2.634 g, 12.71 mmol) and pyridine (2.8 ml, 34.66 mmol) were added to a round bottomed flask at 20-25° C. under nitrogen atmosphere, and the resulting mixture was stirred at r.t. for 0.5 h, then cooled to 0-5° C. while stirring. Pivaloyl chloride (2.1 ml, 17.32 mmol) was added dropwise while keeping the temperature below 5° C., and the mixture was further stirred for 1 h at 0-5° C. A solution of methyl 2-chloro-6-methylamino-benzoate (II) (2.3064 g, 11.55 mmol) in anhydrous dichloromethane (11 ml) was prepared and added to the reaction at 0° C. The reaction was allowed to warm up to r.t. and stirred at this temperature for 14 h, then concentrated under reduced pressure. Ethyl acetate (180 ml) and a solution of 0.1N HCl (80 ml) were added, the phases were mixed and the aqueous phase was discharged. The wash steps with 0.1N HCl (80 ml) was repeated twice more, then the reaction was washed twice with 80 ml brine and three times with 80 ml NaHCO3. The organic phases were dried over sodium sulfate and filtered and the solvent was removed under reduced pressure to afford a residue, which was recrystallized from isopropanol to obtain an off-white solid. Yield: 80%. The purity of the isolated product was 100% (HPLC, area %).

1. temperaturecooled to 0-5° C.
2. stirringwhile stirring
3. customthe temperature below 5° C.
4. stirringthe mixture was further stirred for 1 h at 0-5° C
5. additionadded to the reaction at 0° C
6. temperatureto warm up to r.t.
7. stirringstirred at this temperature for 14 h
8. concentrationconcentrated under reduced pressure
9. additionEthyl acetate (180 ml) and a solution of 0.1N HCl (80 ml) were added
10. additionthe phases were mixed
11. washthe reaction was washed twice with 80 ml brine and three times with 80 ml NaHCO3
12. dry with materialThe organic phases were dried over sodium sulfate
13. filtrationfiltered
14. customthe solvent was removed under reduced pressure
15. customto afford a residue, which
16. customwas recrystallized from isopropanol
17. customto obtain an off-white solid

ORD record

ord-e7f0584e064f4f49aadee79759498a53

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865742B2