Dimethylformamide → 3-[4-(2-Trifluoromethylsulfanyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide

HRID 929768Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 929768
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH2:15])=[O:14])[O:10][N:9]=2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[F:22][C:23]([F:34])([F:33])[S:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27]Br.CN(C=O)C>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:22][C:23]([S:24][C:25]1[CH:32]=[CH:31][CH:30]=[CH:29][C:26]=1[CH2:27][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([C:13]([NH2:15])=[O:14])[O:10][N:9]=2)=[CH:6][CH:7]=1)([F:34])[F:33]

Komponenten

7

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27778762-((Trifluoromethyl)thio)benzyl bromideHCID 1364912503-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide2×

Produkt 1

HCID 762841003-[4-(2-Trifluoromethylsulfanyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

3-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide (which may be prepared as described in Preparation of Intermediate 2; 60 mg, 0.30 mmol) was dissolved in THF (1.5 mL). K2CO3 (41 mg, 0.30 mmol) and tetrabutylammonium iodide (15 mg, 0.04 mmol) were added. 2-(Trifluoromethylthio)benzyl bromide (available from Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA; 88 μL, 0.30 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 h. DMF (100 μL) was added and the mixture was heated at 45° C. for 4 h. The reaction mixture was cooled to room temperature and partitioned between EtOAc (5 mL) and H2O (5 mL). The organic layer was evaporated and the residue was purified by chromatography (35-50% EtOAc/hexanes) to give 3-[4-(2-trifluoromethylsulfanyl-benzyloxy)-phenyl]-isoxazole-5-carboxylic acid amide (60 mg, 52%) as a white solid. HRMS Calcd. for C18H14F3N2O3S (M+H)+, 395.0672. Found: 395.0688.

Aufarbeitung

  1. temperaturethe mixture was heated at 45° C. for 4 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompartitioned between EtOAc (5 mL) and H2O (5 mL)
  4. customThe organic layer was evaporated
  5. customthe residue was purified by chromatography (35-50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-b283eb686ba84f6d94a0ac0e35233c71
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296711B2

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