Water → 2-[4-(1H-Imidazol-1-yl)phenoxy]-N-(phenylmethyl)ethanamine dihydrochloride

HRID 728817Notes

Reaction equation

HRID 728817 reaction equation
[H-].[Na+].[N:3]1([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH:7]=[CH:6][N:5]=[CH:4]1.[ClH:15].[CH2:16]([NH:23][CH2:24][CH2:25][Cl:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O>CN(C=O)C>[ClH:26].[ClH:15].[N:3]1([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:25][CH2:24][NH:23][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:10][CH:9]=2)[CH:7]=[CH:6][N:5]=[CH:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 823151-(p-Hydroxyphenyl)imidazoleHCID 13054189Benzenemethanamine, N-(2-chloroethyl)-, hydrochloride (1:1)

Product 1

HCID 676898452-[4-(1H-Imidazol-1-yl)phenoxy]-N-(phenylmethyl)ethanamine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 39.5 g (0.82 mol) sodium hydride in 500 mL DMF add 37.3 g (0.233 mol) 4-(1H-imidazol-yl)phenol portionwise. Chill the reaction mixture on an ice/MeOH bath during the addition. After addition, stir the reaction mixture at room temperature until gas evolution ceases. After this time, return the reaction mixture to the ice bath and add 50.2 g (0.29 g) N-benzyl-2-chloroethylamine hydrochloride portionwise. After addition is complete, heat the stirring suspension to 65° C. Followthe progress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1). At the completion of the reaction, cool to room temperature and slowly add 20 mL H2O. Remove the solidsby suction filtration and evaporate the solvents. Chromatograph the resulting oil on silica gel using (CH2Cl2 :MeOH, 98:2), to isolate the title compound as the free base. Dissolve the free base in excess 3 M methanolic HCl and evaporate the solvents to give the title compound.

Workup

  1. temperatureChill the reaction mixture on an ice/MeOH bath
  2. additionduring the addition
  3. additionAfter addition
  4. additionAfter addition
  5. temperatureheat the stirring suspension to 65° C
  6. customprogress of the reaction by thin-layer chromatography on silica gel (methylene chloride:methanol, 9:1)
  7. customAt the completion of the reaction
  8. temperaturecool to room temperature
  9. customRemove
  10. filtrationthe solidsby suction filtration
  11. customevaporate the solvents

Sources & evidence

ORD record
ord-5e108f65339648f5968abb1db63b90ec
Source dataset
uspto-grants-1991_09
Patent number
US05051423

Reaction notes

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