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

HRID 929768Notes

Reaction equation

HRID 929768 reaction equation
[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]

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b283eb686ba84f6d94a0ac0e35233c71
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

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