Sodium hydride → Tert-butyl(r)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)benzoyl]piperazine-1-carboxylate

HRID 856223Notes

Reaction equation

HRID 856223 reaction equation
[OH:1][C:2]1[CH:22]=[CH:21][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:26]1[N:27]([CH2:34][C@:35]2([CH3:38])[CH2:37][O:36]2)[CH:28]=[C:29]([N+:31]([O-:33])=[O:32])[N:30]=1>CN(C=O)C>[CH3:37][C@@:35]1([CH2:38][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:6]([N:8]3[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])[CH2:12][CH2:13]3)=[O:7])=[CH:21][CH:22]=2)[O:36][C:26]2=[N:30][C:29]([N+:31]([O-:33])=[O:32])=[CH:28][N:27]2[CH2:34]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 23081232Tert-butyl 4-(4-hydroxybenzoyl)piperazine-1-carboxylate

Product 1

HCID 69635347Tert-butyl(r)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)benzoyl]piperazine-1-carboxylateYield 70.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Tert-butyl 4-(4-hydroxybenzoyl)piperazine-1-carboxylate (6.6 g, 21.5 mmol) was dissolved in DMF (50 ml). To the solution, sodium hydride (991 mg, 24.8 mmol) was added at room temperature, and the solution was stirred for 20 minutes at 80° C. To the solution, (R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 12 (5.16 mg, 23.7 mmol) was added with cooling on ice-bath, and the solution was stirred for further 20 minutes at 80° C. To the reaction mixture, ice-water was added, and the solution was stirred vigorously. The precipitates were filtered off, washed with water, dissolved in methylene chloride. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) and then crystallized from methylene chloride-diisopropyl ether to afford tert-butyl (R)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)benzoyl]piperazine-1-carboxylate (7.35 g, yield 70%) as a white powder.

Workup

  1. temperaturewith cooling on ice-bath
  2. stirringthe solution was stirred for further 20 minutes at 80° C
  3. stirringthe solution was stirred vigorously
  4. filtrationThe precipitates were filtered off
  5. washwashed with water
  6. dissolutiondissolved in methylene chloride
  7. washThe organic phase was washed with a saturated saline solution
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe resulting filtrate was concentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1)
  12. customcrystallized from methylene chloride-diisopropyl ether

Sources & evidence

ORD record
ord-475d3c7a0d684e4abf9f2ae5d09bab7f
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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