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

HRID 929768노트

반응식

HRID 929768 반응식
[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]

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 27778762-((Trifluoromethyl)thio)benzyl bromideHCID 1364912503-(4-Hydroxy-phenyl)-isoxazole-5-carboxylic acid amide2회

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b283eb686ba84f6d94a0ac0e35233c71
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296711B2

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