Potassium Carbonate → 5-Fluoro-2-(3-methyl-benzo[d]isoxazol-6-yloxy)-benzonitrile

HRID 2112167Notes

Reaction equation

HRID 2112167 reaction equation
[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([OH:11])=[CH:10][C:5]=2[O:4][N:3]=1.F[C:13]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=1[C:15]#[N:16].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O>[F:21][C:18]1[CH:19]=[CH:20][C:13]([O:11][C:9]2[CH:8]=[CH:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH:10]=2)=[C:14]([CH:17]=1)[C:15]#[N:16]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1235582,5-DifluorobenzonitrileHCID 1354978903-Methyl-1,2-benzisoxazol-6-ol

Product 1

HCID 574841185-Fluoro-2-(3-methyl-benzo[d]isoxazol-6-yloxy)-benzonitrileYield 58%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

3-Methyl-benzo[d]isoxazol-6-ol (1v) (reference for synthesis, see Indian J. Chem. Sect.B; 19:571-575 (1980)) (1.58 g, 10.6 mmol) and 2,5-difluoro-benzonitrile (2v) (1.47 g, 10.6 mmol) were combined with potassium carbonate (1.46 g. 10.6 mmol) in 15 mL of dry DMA. The reaction was heated in a 100° C. bath for 6 hours. The reaction was cooled and diluted with EtOAc (200 mL) and washed three times with water, NH4Cl, NaHCO3, and brine. The organic solution was dried over MgSO4 and concentrated. The crude residue was purified by column chromatography (silica, 70-80% CH2Cl2/hexane) to provide compound (3v) (1.65 g, 58% yield).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed three times with water, NH4Cl, NaHCO3, and brine
  3. dry with materialThe organic solution was dried over MgSO4
  4. concentrationconcentrated
  5. customThe crude residue was purified by column chromatography (silica, 70-80% CH2Cl2/hexane)

Sources & evidence

ORD record
ord-d16d8e781f9a4af7b46fe05f342307d0
Source dataset
uspto-grants-2009_04
Patent number
US07521447B2

Reaction notes

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