Ethyl Acetate → Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate

HRID 2388176Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2388176
Br[CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:20]([O:22][C:23](=[O:37])[CH2:24][NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=1[O:35][CH3:36])[CH3:21].C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>CN(C=O)C.[Cl-].[Na+].O>[CH3:36][O:35][C:28]1[CH:29]=[C:30]([O:33][CH3:34])[CH:31]=[CH:32][C:27]=1[CH2:26][N:25]([CH2:2][C:3]1[C:4]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[N:5][O:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:37]

Komponenten

7

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateHCID 67529002Ethyl 4-(bromomethyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate

Produkt 1

HCID 67530684Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(4-fluorophenyl)isoxazole-5-carboxylateAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

Ethyl 4-(bromomethyl)-3-(4-fluorophenyl)isoxazole-5-carboxylate (12.4 g, 37.8 mmol) was dissolved in 80 mL of DMF. N-(2,4-dimethoxybenzyl)glycine ethyl ester (9.56 g, 37.8 mmol) and potassium carbonate (5.75 g, 41.6 mmol) were added, and the mixture was stirred at room temperature for 16 h. EtOAc (200 mL) and brine (200 mL) were added and the aqueous layer was extracted with additional EtOAc. The combined organic layer was washed with water and brine, and dried over MgSO4. After solvent was removed in vacuo, the crude product was purified by flash chromatography (0-40% EtOAc/hexanes) to give 8.7 g of the title compound. 1H NMR (CDCl3, 200 MHz): δ=8.00-8.13 (m, 2H), 7.01-7.18 (m, 3H), 6.38-6.45 (m, 2H), 4.48 (q, 2H, J=7.4 Hz), 4.00-4.20 (m, 4H), 3.82 (s, 5H), 3.65 (s, 3H), 3.30 (s, 2H), 1.47 (t, 3H, J=7.0 Hz), 1.20-1.30 (m, 3H).

Aufarbeitung

  1. extractionthe aqueous layer was extracted with additional EtOAc
  2. washThe combined organic layer was washed with water and brine
  3. dry with materialdried over MgSO4
  4. customAfter solvent was removed in vacuo
  5. customthe crude product was purified by flash chromatography (0-40% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-5b3995b2089947a8b854d1caa01a6bce
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08269008B2

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