Water → 3-Chloro-alpha-[[[2-[4-((4,5-dihydro-1H-2-imidazolyl)methyloxy)phenyl]-1-methylethyl]amino]methyl]benzenemethanol, dihydrochloride

HRID 465427Notes

Reaction equation

HRID 465427 reaction equation
[NH2:1][CH2:2][CH2:3][NH2:4].C([Al](CC(C)C)CC(C)C)C(C)C.[Cl:18][C:19]1[CH:20]=[C:21]([CH:41]=[CH:42][CH:43]=1)[CH:22]([OH:40])[CH2:23][NH:24][CH:25]([CH3:39])[CH2:26][C:27]1[CH:38]=[CH:37][C:30]([O:31][CH2:32][C:33](OC)=O)=[CH:29][CH:28]=1.O>C1(C)C=CC=CC=1.CCCCCC.CO.ClCCl>[ClH:18].[ClH:18].[Cl:18][C:19]1[CH:20]=[C:21]([CH:22]([CH2:23][NH:24][CH:25]([CH3:39])[CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:31][CH2:32][C:33]3[NH:1][CH2:2][CH2:3][N:4]=3)=[CH:37][CH:38]=2)[OH:40])[CH:41]=[CH:42][CH:43]=1

Participants

9

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 122186Brl 35135HCID 16682931Triisobutylaluminum

Product 1

HCID 1317175683-Chloro-alpha-[[[2-[4-((4,5-dihydro-1H-2-imidazolyl)methyloxy)phenyl]-1-methylethyl]amino]methyl]benzenemethanol, dihydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

1,2-Diaminoethane (0.44 g) in dry toluene (50 ml) was added under nitrogen to a stirred 25% solution of tri-isobutylaluminium (6.5 mmole) in hexane at <10° C. The solution was allowed to attain ambient temperature and a solution of methyl 4-[2-[(3-chloro-β-hydroxyphenethyl) amino]propyl]phenoxyacetate (generated from 2 g of the hydrobromide salt) in toluene (20 ml) added and the mixture heated under reflux for 7 h. The reaction mixture was cooled and decomposed below -5° C. with a mixture of water (2 ml), dichloromethane (6 ml) and methanol (6 ml). This mixture was boiled for 0.5 h, dried (magnesium sulphate) filtered and evaporated. The resulting oil was taken up in ethyl acetate, dried, filtered and evaporated. The resulting oil was treated with ethereal hydrogen chloride 3-chloro-α-[[[2-[4-((4,5-dihydro-1H-2-imidazolyl)methyloxy)phenyl]-1-methylethyl]amino]methyl] benzenemethanol, dihydrochloride m.p. 252°-256° C. (methanol-ether) as a >95:5 mixture of diastereoisomers.

Workup

  1. customto attain ambient temperature
  2. temperaturethe mixture heated
  3. temperatureunder reflux for 7 h
  4. temperatureThe reaction mixture was cooled
  5. dry with materialdried (magnesium sulphate)
  6. filtrationfiltered
  7. customevaporated
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. additionThe resulting oil was treated with ethereal hydrogen chloride 3-chloro-α-[[[2-[4-((4,5-dihydro-1H-2-imidazolyl)methyloxy)phenyl]-1-methylethyl]amino]methyl] benzenemethanol, dihydrochloride m.p. 252°-256° C. (methanol-ether) as a >95:5 mixture of diastereoisomers

Sources & evidence

ORD record
ord-b0dc6a6dfb3044979e0a5e69b93e0448
Source dataset
uspto-grants-1992_10
Patent number
US05153210

Reaction notes

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