Sodium hydride → tert-butyl (R)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-carboxylate

HRID 856304Notes

Reaction equation

HRID 856304 reaction equation
Cl[C:2]1[N:3]([CH2:10][C@@:11]([OH:27])([CH3:26])[CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[H-].[Na+]>O1CCOCC1>[CH3:26][C@:11]1([CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[O:27][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 69635160HCID 69635160, compound

Product 1

HCID 69635188tert-butyl (R)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Tert-butyl (R)-4-[3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl]-piperazine-1-carboxylate prepared in Example 368 (376 mg, 0.93 mmol) was dissolved in 1,4-dioxane (10 ml). To the solution, sodium hydride (45 mg, 1.12 mmol) was added with cooling on ice-bath, and the resulting solution was stirred at room temperature for 30 minutes and then stirred under reflux for 24 hours. The reaction mixture was allowed to return to room temperature and concentrated under reduced pressure. To the residue, water was added slowly, and the solution was extracted with ethyl acetate twice. The organic phase was dried over sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/acetone=3/1) to afford tert-butyl (R)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-carboxylate (239 mg, yield 70%) as a white powder.

Workup

  1. temperaturewith cooling on ice-bath
  2. stirringstirred
  3. temperatureunder reflux for 24 hours
  4. customto return to room temperature
  5. concentrationconcentrated under reduced pressure
  6. additionTo the residue, water was added slowly
  7. extractionthe solution was extracted with ethyl acetate twice
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (n-hexane/acetone=3/1)

Sources & evidence

ORD record
ord-9a98c65e3f394b86a548f1a3c9457a4e
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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