1,2-Dichloroethane → (R)-carbamic acid 3-[4-(4-chloro-phenyl)-piperazin-1-yl]-3-oxo-1-phenyl-propyl ester

온도

25 °C

(R)-3-hydroxy-3-phenylpropionic acid (1.0 g, 6.0 mmole) and 4-chloro phenylpiperazine (1.18 g, 6.0 mmole) were dissolved in 50 mL of solvent ‘tetrahydrofuran’ at a room temperature, and EDC (1.24 g, 6.0 mmole) and HOBt (0.81 g, 6 mmole) were added dropwise to the mixture. Then, the resulting mixture was stirred at 25° C. for 5 hours. The mixture was distilled under a reduced pressure to remove excessive solvents, and the solvent-free mixture was neutralized with 1 normal aqueous sodium chloride solution (20 mL), and 25 mL of ethyl acetate was added to the resulting mixture to separate an organic phase. Then, the prepared organic phase was further extracted twice with 15 mL of ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate (2 g), and filtered, and the resulting filtrate was concentrated under a reduced pressure, and separated and purified with column chromatography (hexane:ethyl acetate=1:1 to 1:10). The resulting reaction product (0.345 g, 1 mmol) was dissolved in tetrahydrofuran (15 mL), and 1,1′-carbodiimidazole (0.325 g, 2 mmol) was then added to the reaction product, and the resulting reaction mixture was stirred at a room temperature for 1 hour. Then, excessive aqueous ammonium hydroxide was added to the reaction mixture, and resulting reaction mixture was stirred at a room temperature for additional 2 hours. The reaction mixture was diluted with water, and extracted several times with ethyl acetate to obtain an organic phase. The prepared organic phase was dried over magnesium sulfate, and concentrated under a reduced pressure. The resulting pellet was purified with column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate) to obtain a title compound.

1. distillationThe mixture was distilled under a reduced pressure
2. customto remove excessive solvents
3. additionwas added to the resulting mixture
4. customto separate an organic phase
5. extractionThen, the prepared organic phase was further extracted twice with 15 mL of ethyl acetate
6. dry with materialThe organic phase was dried over anhydrous magnesium sulfate (2 g)
7. filtrationfiltered
8. concentrationthe resulting filtrate was concentrated under a reduced pressure
9. customseparated
10. custompurified with column chromatography (hexane:ethyl acetate=1:1 to 1:10)
11. customthe resulting reaction mixture
12. stirringwas stirred at a room temperature for 1 hour
13. customresulting
14. customreaction mixture
15. stirringwas stirred at a room temperature for additional 2 hours
16. extractionextracted several times with ethyl acetate
17. customto obtain an organic phase
18. dry with materialThe prepared organic phase was dried over magnesium sulfate
19. concentrationconcentrated under a reduced pressure
20. customThe resulting pellet was purified with column chromatography (hexane:ethyl acetate=1:1 to ethyl acetate)

ORD 기록

ord-e029667d8b334e57a6f01c401f8b81ff

출처 데이터셋

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08901116B2