Water → HCID 69481512, compound

HRID 856258Notes

Reaction equation

HRID 856258 reaction equation
Cl[C:2]1[N:3]([CH2:10][C@:11]2([CH3:14])[CH2:13][O:12]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:18][CH:17]=1.O.[H-].[Na+]>CN(C=O)C>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH2:24][O:25][CH:26]2[CH2:27][CH2:28][N:29]([CH2:13][C@:11]3([CH3:14])[O:12][C:2]4=[N:6][C:5]([N+:7]([O-:9])=[O:8])=[CH:4][N:3]4[CH2:10]3)[CH2:30][CH2:31]2)=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 24758Sodium hydrideHCID 10443353(R)-2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazoleHCID 69481274HCID 69481274, compound

Product 1

HCID 69481512HCID 69481512, compoundYield 19.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

(R)-2-Chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 12 (0.103 g, 0.473 mmol) and 4-[3-(4-chlorophenyl)propoxy]piperidine (0.109 g, 0.430 mmol) were dissolved in DMF (10 ml), and the solution was stirred at 60° C. for 4 hours. The reaction mixture was added water and extracted with ethyl acetate. The organic phase was combined, washed with water and a saturated saline solution, dried over sodium sulfate and then filtered. The resulting filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/3) to afford an oil. The oil was dissolved in DMF (2 ml). To the solution, sodium hydride (15 mg, 0.375 mmol) was added with cooling on ice-bath followed by stirring at room temperature for 3 hours. To the reaction mixture, water was added, and the precipitates were filtered off, purified by silica gel column chromatography (methylene chloride/ethyl acetate=6/1) and then recrystallized from ethyl acetate/n-hexane=1/3 (6 ml) to afford (S)-2-{4-[3-(4-chlorophenyl)propoxy]-piperidin-1-ylmethyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (36 mg, yield 19%) as a white powder.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with water
  3. dry with materiala saturated saline solution, dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe resulting filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=2/3)
  7. customto afford an oil
  8. temperaturewith cooling on ice-bath
  9. stirringby stirring at room temperature for 3 hours
  10. filtrationthe precipitates were filtered off
  11. custompurified by silica gel column chromatography (methylene chloride/ethyl acetate=6/1)
  12. customrecrystallized from ethyl acetate/n-hexane=1/3 (6 ml)

Sources & evidence

ORD record
ord-1e382f0087c349fdb016c7e4b8d28a43
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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