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

HRID 856206Notes

Reaction equation

HRID 856206 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C@@:20]([OH:32])([CH3:31])[CH2:21][N:22]3[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[N:24]=[C:23]3Cl)=[O:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[H-].[Na+]>CN(C=O)C>[F:1][C:2]([F:34])([F:33])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH2:19][C@:20]3([CH3:31])[O:32][C:23]4=[N:24][C:25]([N+:27]([O-:29])=[O:28])=[CH:26][N:22]4[CH2:21]3)=[O:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 69479082(R)-3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl 4-(4-trifluoromethylphenylamino)piperidine-1-carboxylate

Product 1

HCID 69481331(R)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl 4-(4-trifluoromethylphenylamino)piperidine-1-carboxylateYield 31.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the solution of (R)-3-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxy-2-methylpropyl 4-(4-trifluoromethylphenylamino)piperidine-1-carboxylate prepared in Example 105 (1.44 g, 2.85 mmol) in DMF (10 ml), sodium hydride (0.14 g, 3.42 mmol) was added followed by stirring for 1 hour with cooling on ice-bath. To the reaction mixture, ice-water was added, and the solution was extracted with ethyl acetate. The organic phase was washed with water, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from acetonitrile-isopropanol to afford (R)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl 4-(4-trifluoromethylphenylamino)piperidine-1-carboxylate (0.42 g, yield 31%) as a white solid.

Workup

  1. temperaturewith cooling on ice-bath
  2. extractionthe solution was extracted with ethyl acetate
  3. washThe organic phase was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate)
  7. customrecrystallized from acetonitrile-isopropanol

Sources & evidence

ORD record
ord-d2a584e0e21b4c779f76cd16dcaee767
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…