Hydrochloric Acid → Ethyl cis(+/-)-2-{3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidin-1-yl}-1,3-thiazole-5-carboxylate

A 4 N hydrochloric acid/ethyl acetate solution (10 mL, 40 mmol) was added to tert-butyl cis(±)-3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidine-1-carboxylate obtained in Example (90e) (0.3 g, 0.75 mmol), and the mixture was stirred at room temperature for 20 minutes. Following concentration under reduced pressure, the residue was dissolved in DMF (8 mL). Diisopropylethylamine (0.45 g, 3.5 mmol) and ethyl 2-bromo-1,3-thiazole-5-carboxylate (0.21 g, 0.9 mmol) were added, and the mixture was stirred at 70° C. for 1.5 hours. Dilute hydrochloric acid was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous sodium magnesium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate) to obtain 0.26 g of the title compound as a light brown solid (76%).

1. concentrationconcentration under reduced pressure
2. dissolutionthe residue was dissolved in DMF (8 mL)
3. stirringthe mixture was stirred at 70° C. for 1.5 hours
4. extractionfollowed by extraction with ethyl acetate
5. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution and brine
6. dry with materialdried over anhydrous sodium magnesium sulfate
7. concentrationconcentration under reduced pressure
8. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=5/1, ethyl acetate)

ORD 기록

ord-7a011b5f13744fb39feef5b78e1986a8

출처 데이터셋

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08927588B2