Sodium hydride → (R)-3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one

HRID 856353Notes

Reaction equation

HRID 856353 reaction equation
Cl[C:2]1[N:3]([CH2:10][C@:11]([OH:31])([CH3:30])[CH2:12][N:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[O:15][C:14]2=[O:29])[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[H-].[Na+]>O1CCOCC1>[CH3:30][C@@:11]1([CH2:12][N:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[O:15][C:14]2=[O:29])[O:31][C:2]2=[N:6][C:5]([N+:7]([O-:9])=[O:8])=[CH:4][N:3]2[CH2:10]1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 69481895(R)-3-[3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl]-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one

Product 1

HCID 69480520(R)-3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-oneYield 40%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-3-[3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl]-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one prepared in Example 539 (0.87 g, 1.88 mmol) in 1,4-dioxane (18 ml), sodium hydride (98 mg, 2.44 mmol) was added with cooling on ice-bath. The mixture was stirred under reflux for 5 hours, concentrated under reduced pressure, then water was added with cooling on ice-bath. The solution was extracted with ethyl acetate, and the organic phase was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate 9/1), and recrystallized from acetonitrile/isopropanol to afford (R)-3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one (0.32 g, yield 40%) as a white powder.

Workup

  1. temperaturewith cooling on ice-bath
  2. temperatureunder reflux for 5 hours
  3. concentrationconcentrated under reduced pressure
  4. additionwater was added
  5. temperaturewith cooling on ice-bath
  6. extractionThe solution was extracted with ethyl acetate
  7. dry with materialthe organic phase was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate 9/1)
  10. customrecrystallized from acetonitrile/isopropanol

Sources & evidence

ORD record
ord-31c32727514d46bfbc16ce3a4da705f6
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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