Sodium hydride → 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 856347Notes

Reaction equation

HRID 856347 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 230815053-[3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl]-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one

Product 1

HCID 230811973-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-oneYield 48%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 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 516 (3.27 g, 7.05 mmol) in 1,4-dioxane (70 ml), sodium hydride (0.37 g, 9.17 mmol) was added with cooling on ice-bath followed by stirring under reflux for 3 hours. The reaction mixture was concentrated under reduced-pressure. To the solution, water was added with cooling on ice-bath, and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=4/1) and recrystallized from acetonitrile-ethanol to afford 3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)-5-(4-trifluoromethoxyphenyl)-3H-[1,3,4]oxadiazol-2-one (1.43 g, yield 48%) as a white solid.

Workup

  1. temperaturewith cooling on ice-bath
  2. temperatureunder reflux for 3 hours
  3. concentrationThe reaction mixture was concentrated under reduced-pressure
  4. additionTo the solution, water was added
  5. temperaturewith cooling on ice-bath
  6. extractionthe mixture was extracted with ethyl acetate
  7. dry with materialThe extract was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (methylene chloride/ethyl acetate=4/1)
  10. customrecrystallized from acetonitrile-ethanol

Sources & evidence

ORD record
ord-b3cfc923b65f4429a17383c08b622c47
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…