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

HRID 856216Notes

Reaction equation

HRID 856216 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH: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)=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:24]1[N:25]([CH2:32][C:33]2([CH3:36])[CH2:35][O:34]2)[CH:26]=[C:27]([N+:29]([O-:31])=[O:30])[N:28]=1>CN(C=O)C>[CH3:35][C:33]1([CH2:36][O:1][C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:12][CH2:13]3)=[CH:4][CH:3]=2)[O:34][C:24]2=[N:28][C:27]([N+:29]([O-:31])=[O:30])=[CH:26][N:25]2[CH2:32]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 159655232-Chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 19381871tert-Butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 23081135Tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylateYield 41.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Tert-butyl 4-(4-hydroxyphenyl)piperidine-1-carboxylate (364 mg, 1.31 mmol) was dissolved in DMF (10 ml). To the solution, sodium hydride (58 mg, 1.44 mmol) was added at room temperature, and the solution was stirred for 20 minutes at 80° C. To the solution, 2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 6 (300 mg, 1.38 mmol) was added with cooling on ice-bath followed by stirring 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 and 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=200/1) and then crystallized from methylene chloride-diisopropyl ether to afford tert-butyl 4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethoxy)phenyl]piperidine-1-carboxylate (248 mg, yield 41%) as a white powder.

Workup

  1. temperaturewith cooling on ice-bath
  2. stirringby stirring 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=200/1)
  12. customcrystallized from methylene chloride-diisopropyl ether

Sources & evidence

ORD record
ord-febb9f0195304efea6e8d8aeac486d8e
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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