Sodium hydride → (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856230Notes

Reaction equation

HRID 856230 reaction equation
[F:1][C:2]([F:25])([F:24])[O:3][C:4]1[CH:23]=[CH:22][C:7]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.[H-].[Na+].Cl[C:29]1[N:30]([CH2:37][C@:38]2([CH3:41])[CH2:40][O:39]2)[CH:31]=[C:32]([N+:34]([O-:36])=[O:35])[N:33]=1>CN(C=O)C>[CH3:40][C@@:38]1([CH2:41][O:21][C:18]2[CH:19]=[CH:20][C:15]([N:12]3[CH2:13][CH2:14][N:9]([CH2:8][C:7]4[CH:22]=[CH:23][C:4]([O:3][C:2]([F:1])([F:24])[F:25])=[CH:5][CH:6]=4)[CH2:10][CH2:11]3)=[CH:16][CH:17]=2)[O:39][C:29]2=[N:33][C:32]([N+:34]([O-:36])=[O:35])=[CH:31][N:30]2[CH2:37]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 307469694-[4-(4-Trifluoromethoxybenzyl)piperazin-1-yl]phenol

Product 1

HCID 10459740(R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-[4-(4-Trifluoromethoxybenzyl)piperazin-1-yl]phenol (3.36 g, 9.54 mmol) was dissolved in of DMF (20 ml). To the solution, sodium hydride (420 mg, 10.5 mmol) was added at room temperature, and the solution was stirred for 15 minutes at 80° C. To the reaction mixture, (R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 12 (2.18 g, 10.0 mmol) was added with cooling on ice-bath followed by stirring for further 15 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 solution 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-ethyl acetate to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxybenzyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (2.0 g, yield 40%) as a light yellow powder.

Workup

  1. temperaturewith cooling on ice-bath
  2. stirringby stirring for further 15 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 solution 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-ethyl acetate

Sources & evidence

ORD record
ord-78be1402b2c544aab2d5a09a2c28082a
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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