Water → (S)-2-methyl-6-nitro-2-{4-[1-(4-trifluoromethoxyphenyl)piperidin-4-yl]piperazin-1-ylmethyl}-2,3-dihydroimidazo[2,1-b]oxazole

HRID 856380Notes

Reaction equation

HRID 856380 reaction equation
Br[C:2]1[N:3]([CH2:10][C@@:11]([CH3:37])([OH:36])[CH2:12][N:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[H-].[Na+].C(OCC)(=O)C.O>CN(C)C=O>[CH3:37][C@@:11]1([CH2:12][N:13]2[CH2:18][CH2:17][N:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]4[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)[O:36][C:2]2=[N:6][C:5]([N+:7]([O-:9])=[O:8])=[CH:4][N:3]2[CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 69481648(S)-1-(2-bromo-4-nitroimidazol-1-yl)-2-methyl-3-{4-[1-(4-trifluoromethoxyphenyl)piperidin-4-yl]piperazin-1-yl}propan-2-ol

Product 1

HCID 69482526(S)-2-methyl-6-nitro-2-{4-[1-(4-trifluoromethoxyphenyl)piperidin-4-yl]piperazin-1-ylmethyl}-2,3-dihydroimidazo[2,1-b]oxazoleYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-1-(2-bromo-4-nitroimidazol-1-yl)-2-methyl-3-{4-[1-(4-trifluoromethoxyphenyl)piperidin-4-yl]piperazin-1-yl}propan-2-ol (790 mg, 1.34 mmol) was dissolved in N,N-dimethylformamide (4 ml), sodium hydride (69 mg, 1.74 mmol) was added while cooling on ice, and the solution was stirred at the same temperature for 1 hour. To the reaction mixture, ethyl acetate (1.3 ml) and water (10 ml) were added in this order, and the precipitated crystals were filtered off and washed with water. The crystals were purified by silica gel column chromatography (methylene chloride/methanol=10/1) and recrystallized from ethyl acetate/isopropyl ether to obtain (S)-2-methyl-6-nitro-2-{4-[1-(4-trifluoromethoxyphenyl)piperidin-4-yl]piperazin-1-ylmethyl}-2,3-dihydroimidazo[2,1-b]oxazole (270 mg, yield 40%) as a white powder.

Workup

  1. temperaturewhile cooling on ice
  2. filtrationthe precipitated crystals were filtered off
  3. washwashed with water
  4. customThe crystals were purified by silica gel column chromatography (methylene chloride/methanol=10/1)
  5. customrecrystallized from ethyl acetate/isopropyl ether

Sources & evidence

ORD record
ord-f410d5fe8e3b41a285d2af39881f00b6
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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