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

HRID 856221Notes

Reaction equation

HRID 856221 reaction equation
[F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.[H-].[Na+].Cl[C:28]1[N:29]([CH2:36][C@:37]2([CH3:40])[CH2:39][O:38]2)[CH:30]=[C:31]([N+:33]([O-:35])=[O:34])[N:32]=1>CN(C=O)C>[CH3:39][C@@:37]1([CH2:40][O:22][C:19]2[CH:20]=[CH:21][C:16]([N:13]3[CH2:14][CH2:15][N:10]([C:7]4[CH:8]=[CH:9][C:4]([O:3][C:2]([F:1])([F:23])[F:24])=[CH:5][CH:6]=4)[CH2:11][CH2:12]3)=[CH:17][CH:18]=2)[O:38][C:28]2=[N:32][C:31]([N+:33]([O-:35])=[O:34])=[CH:30][N:29]2[CH2:36]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 694797194-[4-(4-Trifluoromethoxyphenyl)piperazin-1-yl]phenol

Product 1

HCID 69481385(R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxyphenyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 39.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

4-[4-(4-Trifluoromethoxyphenyl)piperazin-1-yl]phenol (1.7 g, 5.02 mmol) was dissolved in DMF (20 ml). To the solution, sodium hydride (221 mg, 5.53 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 (1.2 g, 5.53 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 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/ethyl acetate=10/1) and then recrystallized from ethyl acetate to afford (R)-2-methyl-6-nitro-2-{4-[4-(4-trifluoromethoxyphenyl)piperazin-1-yl]phenoxymethyl}-2,3-dihydroimidazo[2,1-b]oxazole (1.02 g, yield 39%) as a light yellow 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 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/ethyl acetate=10/1)
  12. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-701f0eff92144f3d96b86b33e38dde40
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…