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

HRID 1425030

Reaktionsgleichung

Reaktionsgleichung von HRID 1425030
Cl.C(OCC)(=O)C.[CH2:8]([O:15][C@H:16]1[C@@H:21]([NH:22][C:23]([C:25]2[NH:26][CH:27]=[CH:28][N:29]=2)=[O:24])[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.Br[C:47]1[S:48][C:49]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[CH:50][N:51]=1.Cl>>[CH2:8]([O:15][C@H:16]1[C@@H:21]([NH:22][C:23]([C:25]2[NH:26][CH:27]=[CH:28][N:29]=2)=[O:24])[CH2:20][CH2:19][N:18]([C:47]2[S:48][C:49]([C:52]([O:54][CH2:55][CH3:56])=[O:53])=[CH:50][N:51]=2)[CH2:17]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Komponenten

6

Edukt 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 3614103Ethyl 2-bromothiazole-5-carboxylateHCID 21866389Hydrogen chloride-ethyl acetateHCID 86648572tert-Butyl cis(+/-)-3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidine-1-carboxylate

Produkt 1

HCID 86648573Ethyl cis(+/-)-2-{3-(benzyloxy)-4-[(1H-imidazol-2-ylcarbonyl)amino]piperidin-1-yl}-1,3-thiazole-5-carboxylateAusbeute 76,1 %

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-7a011b5f13744fb39feef5b78e1986a8
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08927588B2

Verknüpfte Notizen

Wird geladen…