Hydrochloric Acid → 1-[[[4-(1H-Imidazol-1-yl)phenyl]methyl]amino]-3-(2-methylphenoxy)-2-propanol dihydrochloride

HRID 728836

Reaction equation

HRID 728836 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][NH2:13])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.C[Si](C)(C)N[Si](C)(C)C.[O:23]1[CH:25]([CH2:26][O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[CH3:34])[CH2:24]1.[ClH:35].[OH-].[Na+]>CS(C)=O.O>[ClH:35].[ClH:35].[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([CH2:12][NH:13][CH2:24][CH:25]([OH:23])[CH2:26][O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:34])=[CH:10][CH:11]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 13838HexamethyldisilazaneHCID 14798Sodium HydroxideHCID 16640o-CRESYL GLYCIDYL ETHERHCID 147398884-(Imidazol-1-yl)benzylamine

Product 1

HCID 676899071-[[[4-(1H-Imidazol-1-yl)phenyl]methyl]amino]-3-(2-methylphenoxy)-2-propanol dihydrochloride

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

Dissolve 1.74 g (10.04 mmol) of 4-(1H-imidazol-1-yl)-benzenemethanamine in 20 mL of dry DMSO under nitrogen. Add 2.44 mL (11.55 mmol) of hexamethyldisilazane and stir at room temperature for 30 min. After this time, add a solution of 1.73 g (10.54 mmol) of 1,2-epoxy-3-(2-methylphenoxy)propane in 10 mL of DMSO and heat in an oil bath at 60° C. for 42 h. Follow the progress of the reaction by thin-layer chromatography on silica gel (acetonitrile: ammonia (aq), 90:10). At the completion of the reaction, add 6 N hydrochloric acid to pH=1 and then add 4 N sodium hydroxide to pH=12. Dilute this basic mixturewith 20 mL of water and extract with 3×75 mL of methylene chloride. Remove the solvent on the rotary evaporator. Purify this residue by flash chromatography using flash silica gel (Baker) and eluting with a solution of acetonitrile: ammonia hydroxide 98:2. Combine pure fractions and removethe solvent on the rotary evaporator. Dissolve this residue in 50 mL of acetonitrile and remove the solvent on the rotary evaporator. Dissolve this residue in 10 mL of methanol and bubble hydrogen chloride through thesolution until pH=1 is reached. Remove the solvent on the rotary evaporatorand recrystallize the solid from 20 mL of isopropanol to provide the title compound.

Workup

  1. temperatureheat in an oil bath at 60° C. for 42 h
  2. customthe progress of the reaction by thin-layer chromatography on silica gel (acetonitrile: ammonia (aq), 90:10)
  3. customAt the completion of the reaction
  4. extractionextract with 3×75 mL of methylene chloride
  5. customRemove the solvent
  6. customon the rotary evaporator
  7. customPurify this residue by flash chromatography
  8. washeluting with a solution of acetonitrile: ammonia hydroxide 98:2
  9. customCombine pure fractions and removethe solvent on the rotary evaporator
  10. dissolutionDissolve this residue in 50 mL of acetonitrile
  11. customremove the solvent
  12. customon the rotary evaporator
  13. dissolutionDissolve this residue in 10 mL of methanol
  14. custombubble hydrogen chloride through thesolution until pH=1
  15. customRemove the solvent on the rotary evaporatorand
  16. customrecrystallize the solid from 20 mL of isopropanol

Sources & evidence

ORD record
ord-7714465f0331494c892e535d29bba125
Source dataset
uspto-grants-1991_09
Patent number
US05051423

Linked notes

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