Water → HCID 25118341, compound

HRID 2400569Notes

Reaction equation

HRID 2400569 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].I[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:20]=[C:19]([C:21]3[CH:25]=[C:24]([CH3:26])[N:23]([CH2:27][C:28]4[CH:33]=[CH:32][C:31]([CH3:34])=[CH:30][CH:29]=4)[N:22]=3)[O:18][N:17]=2)=[CH:12][CH:11]=1.O>CN(C=O)C.[Cu]I.C(OCC)(=O)C>[CH3:26][C:24]1[N:23]([CH2:27][C:28]2[CH:29]=[CH:30][C:31]([CH3:34])=[CH:32][CH:33]=2)[N:22]=[C:21]([C:19]2[O:18][N:17]=[C:16]([C:13]3[CH:14]=[CH:15][C:10]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[CH:11][CH:12]=3)[N:20]=2)[CH:25]=1

Participants

8

Reactant 4

HCID 962WaterHCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 25118340HCID 25118340, compound

Product 1

HCID 25118341HCID 25118341, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 2,2,2-trifluoroethanol (175 mg, 1.75 mmol) in DMF (2 ml) was added to sodium hydride (117 mg of a 60% suspension in mineral oil, 2.94 mmol). The mixture was stirred at 50° C. for 15 minutes. Then, 3-(4-iodophenyl)-5-[5-methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-1,2,4-oxadiazole (Example 13, 200 mg, 0.44 mmol) and copper(I) iodide (167 mg, 0.88 mmol) were added and the reaction mixture was stirred at 110° C. for one hour. The reaction mixture was cooled and water (100 mL) and ethyl acetate (100 mL) was added. The layers were separated and the organic layer was washed with water and brine and then dried with magnesium sulfate. The solvent was evaporated and the residue was purified, first using preparative HPLC and then via flash chromatography (silica, gradient elution from cyclohexane/ethyl acetate 10:1 to 3:1) to afford the title compound as a white solid (33 mg, 18%): 1H NMR (400 MHz, CDCl3) 8.19 (d, 2H), 7.13 (d, 2H), 7.07 (d, 2H), 7.03 (d, 2H), 6.78 (s, 1H), 5.42 (s, 2H), 4.42 (quart, 2H), 2.32 (s, 3H), 2.26 (s, 3H); ES-MS m/z 429 (MH)+, HPLC RT (Method D) 3.19 min.

Workup

  1. stirringthe reaction mixture was stirred at 110° C. for one hour
  2. temperatureThe reaction mixture was cooled
  3. customThe layers were separated
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried with magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified
  8. washvia flash chromatography (silica, gradient elution from cyclohexane/ethyl acetate 10:1 to 3:1)

Sources & evidence

ORD record
ord-2f3ac93d89d04ba186be9120716dd22a
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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