Methyl iodide → 2-(5-Ethyl-3-phenyl-isoxazol-4-yl)-5-(4-fluoro-2-methoxy-phenyl)-[1,3,4]oxadiazole

HRID 1983138Notes

Reaction equation

HRID 1983138 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH3:18])=[N:11][N:12]=2)=[C:4]([O:25][CH3:26])[CH:3]=1.[CH3:27][Si](C)(C)N[Si](C)(C)C.[K].IC.[Cl-].[NH4+]>CN(C=O)C>[CH2:18]([C:17]1[O:16][N:15]=[C:14]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]=1[C:10]1[O:9][C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[O:25][CH3:26])=[N:12][N:11]=1)[CH3:27]

Participants

6

Reactant 4

HCID 6328Methyl iodide2×HCID 25517Ammonium ChlorideHCID 167226452-(4-Fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazoleHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium salt2×

Product 1

HCID 167228552-(5-Ethyl-3-phenyl-isoxazol-4-yl)-5-(4-fluoro-2-methoxy-phenyl)-[1,3,4]oxadiazoleYield 1.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-fluoro-2-methoxy-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (1.00 g, 2.85 mmol) in DMF (10 mL) was added potassium hexamethyldisilazane (0.91 M in tetrahydrofuran, 3.44 mL, 3.13 mmol) at ambient temperature and the resulting mixture was stirred for 1 h. After addition of iodomethane (0.20 mL, 3.13 mmol) the reaction mixture was stirred for 20 h at this temperature. Further potassium hexamethyldisilazane (0.91 M in tetrahydrofuran, 3.44 mL, 3.13 mmol) and iodomethane (0.20 mL, 3.13 mmol) were added and stirring was continued for another 1.5 h. The reaction mixture was poured onto aqueous ammonium chloride (saturated, 50 mL) and was extracted with ethyl acetate. Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 0:80:20) afforded the title compound (14 mg, 1%) as a white solid. MS: m/e=366.1 [M+H]+.

Workup

  1. stirringwas stirred for 20 h at this temperature
  2. stirringstirring
  3. waitwas continued for another 1.5 h
  4. extractionwas extracted with ethyl acetate
  5. dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate:dichloromethane=70:10:20 to 0:80:20)

Sources & evidence

ORD record
ord-7ccf6d10434249d3adaf9ef1d7f084ae
Source dataset
uspto-grants-2009_06
Patent number
US07541372B2

Reaction notes

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