1,2-Dichloroethane → (E)-3-{5-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-pyridin-2-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide

HRID 885894Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 885894
C(O[C:6](=[O:27])/[CH:7]=[CH:8]/[C:9]1[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][OH:26])=[CH:21][CH:20]=2)=[O:18])=[CH:11][N:10]=1)(C)(C)C.C(O)(C(F)(F)F)=O.[OH-].[K+].Cl.CCOCC.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:57][O:58][CH:59]1[CH2:64][CH2:63][CH2:62][CH2:61][O:60]1>C(Cl)Cl.CCO.O.CN(C=O)C>[OH:26][CH2:25][C:22]1[CH:21]=[CH:20][C:19]([C:17](=[O:18])/[CH:16]=[CH:15]/[C:12]2[CH:13]=[CH:14][C:9](/[CH:8]=[CH:7]/[C:6]([NH:57][O:58][CH:59]3[CH2:64][CH2:63][CH2:62][CH2:61][O:60]3)=[O:27])=[N:10][CH:11]=2)=[CH:24][CH:23]=1

Komponenten

12

Edukt 7

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 14797Potassium HydroxideHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 10953452Ether hydrochlorideHCID 67049926(E)-3-{5-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-pyridin-2-yl}-acrylic acid tert-butyl ester

Produkt 1

HCID 86641375(E)-3-{5-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-pyridin-2-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamideAusbeute 29,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of (E)-3-{5-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-pyridin-2-yl}-acrylic acid tert-butyl ester (700 mg, 1.92 mmol) and TFA (2.9 ml) in DCM (10 ml) was stirred at room temperature for 3 h and then the solvent was evaporated in vacuo. The resulting yellow solid was treated with a solution of KOH (240 mg, 4.28 mmol) in EtOH (30 ml) for 30 min. The mixture was acidified with HCl/Et2O and the solid was filtered with a buchner funnel. The powder was dissolved in DCM (10 ml), DMF (10 ml) and TEA (1.1 ml, 7.76 mmol), HOBT (524 mg, 3.88 mmol), EDC (741 mg, 3.88 mmol) and NH2OTHP (227 mg, 1.94 mmol) were added. The solution was stirred at room temperature overnight and then diluted with water and extracted twice with DCM. The organic layer was washed with water, dried over Na2SO4 and evaporated in vacuo. The crude reaction mixture was purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.1) to give 230 mg of (E)-3-{5-[(E)-3-(4-hydroxymethyl-phenyl)-3-oxo-propenyl]-pyridin-2-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide.

Aufarbeitung

  1. customthe solvent was evaporated in vacuo
  2. filtrationthe solid was filtered with a buchner funnel
  3. dissolutionThe powder was dissolved in DCM (10 ml)
  4. extractionextracted twice with DCM
  5. washThe organic layer was washed with water
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customThe crude reaction mixture
  9. customwas purified by column chromatography (eluent: DCM/MeOH/NH4OH 95:5:0.1)

Quellen und Nachweise

ORD-Eintrag
ord-6948312dffb04444b9e0e018e8208eb6
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242175B2

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