Triethylamine → Benzyl 4-(2-oxoazepan-1-yl)piperidin-1-carboxylate

Temperatur

0 °C

To a solution of benzyl 4-aminopiperidin-1-carboxylate (1.7 g) and triethylamine (1.1 mL) in THF (40 mL) was added dropwise 5-bromohexanoyl chloride (1.1 mL), and the mixture was stirred at 0° C. for 2 hours. The solvent was distilled off under reduced pressure and the residue was diluted with water, and extracted with ethyl acetate. The extract was washed with an aqueous 5% citric acid solution and a saturated saline solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in DMF (40 mL), and cooled at 0° C., sodium hydride (60% in oil; 0.60 g) was added thereto, and the mixture was stirred at 0° C. for one hour, at room temperature for one hour and at 80° C. for 15 hours. The solvent was distilled off under reduced pressure, the residue was diluted with water, and the solution was acidified with 1N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with water and saturated saline solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1 to 5/1) to obtain the title compound (0.25 g, 10%) as a yellow oil.

1. distillationThe solvent was distilled off under reduced pressure
2. additionthe residue was diluted with water
3. extractionextracted with ethyl acetate
4. washThe extract was washed with an aqueous 5% citric acid solution
5. dry with materiala saturated saline solution, and dried over anhydrous sodium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. dissolutionThe residue was dissolved in DMF (40 mL)
8. temperaturecooled at 0° C.
9. additionsodium hydride (60% in oil; 0.60 g) was added
10. stirringthe mixture was stirred at 0° C. for one hour, at room temperature for one hour and at 80° C. for 15 hours
11. distillationThe solvent was distilled off under reduced pressure
12. additionthe residue was diluted with water
13. extractionextracted with ethyl acetate
14. washThe extract was washed with water and saturated saline solution
15. dry with materialdried over anhydrous sodium sulfate
16. distillationthe solvent was distilled off under reduced pressure
17. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1 to 5/1)

ORD-Eintrag

ord-8135a7c7eccb4f2a822ae27c502aa13d

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07745623B2