Sodium hydride → HCID 70874211, compound

HRID 2172254Notes

Reaction equation

HRID 2172254 reaction equation
[O-]CC.[Na+].Cl[C:6]1[N:7]([CH2:14][CH2:15][C@@H:16]([OH:29])[CH2:17][O:18]S(C2C=CC(C)=CC=2)(=O)=O)[CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[N:10]=1.[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:48]=[CH:47][C:46](O)=[CH:45][CH:44]=2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[H-].[Na+]>CN(C)C=O.O.C(O)C>[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][N:40]([C:43]2[CH:48]=[CH:47][C:46]([O:18][CH2:17][C@@H:16]3[O:29][C:6]4=[N:10][C:9]([N+:11]([O-:13])=[O:12])=[CH:8][N:7]4[CH2:14][CH2:15]3)=[CH:45][CH:44]=2)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 62657Potassium Phosphate, TribasicHCID 2723922Sodium ethoxideHCID 116877404-(4-Hydroxy-phenyl)-piperazine-1-carboxylic acid tert-butyl esterHCID 86709368HCID 86709368, compound

Product 1

HCID 70874211HCID 70874211, compoundYield 20.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

An ethanol solution (3.02 ml) of 20% sodium ethoxide was added to an ethanol solution (30 ml) of toluene-4-sulfonic acid (R)-4-(2-chloro-4-nitroimidazol-1-yl)-2-hydroxybutyl ester (3.00 g), and the mixture was stirred at room temperature for 30 minutes. 4-(4-Hydroxyphenyl)piperazine-1-carboxylic acid tert-butyl ester (2.36 g) and tripotassium phosphate (1.80 g) were added to the reaction mixture and heated under reflux for 4 hours. Water was added to the reaction mixture, followed by extraction with methylene chloride. The organic layer was washed with water and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue thus obtained was dissolved in dimethylformamide (46 ml), sodium hydride (0.31 g) was added thereto, and the resulting mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, followed by extraction with methylene chloride. The organic layer was dried over magnesium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride:ethyl acetate=1:0→methylene chloride:ethyl acetate=0:1) and recrystallized from acetone to afford the title compound as a yellow powder (0.72 g).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 4 hours
  3. extractionfollowed by extraction with methylene chloride
  4. washThe organic layer was washed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter filtering
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue thus obtained
  9. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  10. extractionfollowed by extraction with methylene chloride
  11. dry with materialThe organic layer was dried over magnesium sulfate
  12. filtrationAfter filtering
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (methylene chloride:ethyl acetate=1:0→methylene chloride:ethyl acetate=0:1)
  15. customrecrystallized from acetone

Sources & evidence

ORD record
ord-9374b79f1082460eab282e1ab6169638
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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