Diethyl Ether → N-[2-(4-benzyloxyphenyl)-1-methylethyl]-2-hydroxy-2-(3-chlorophenyl)ethanamine

HRID 1731569Notes

Reaction equation

HRID 1731569 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](=O)[CH3:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:19][CH:20]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1)[CH2:21][NH2:22].C(OCC)C.CCCCCC>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:22][CH2:21][CH:20]([OH:19])[C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH3:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 8058HexaneHCID 5612534-BenzyloxyphenylacetoneHCID 37516012-Amino-1-(3-chlorophenyl)ethan-1-ol

Product 1

HCID 18628023N-[2-(4-benzyloxyphenyl)-1-methylethyl]-2-hydroxy-2-(3-chlorophenyl)ethanamine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-(4-Benzyloxyphenyl)propan-2-one (2.28 g) was added to a solution of 2-hydroxy-2-(3-chlorophenyl)ethanamine (1.75 g) in dry toluene (100 ml) and the solution was boiled under reflux for 90 minutes in an apparatus incorporating a water-trap. The solution was cooled and the solvent removed under reduced pressure. The residue, dissolved in methanol (100 ml), was cooled to less than 10° C. and treated portionwise with sodium borohydride (3.0 g) over 30 minutes, with stirring. The mixture was stirred for one hour at room temperature and the solvent removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried (magnesium sulphate), filtered and evaporated to dryness to give a solid. Trituration of the solid with diethyl ether followed by addition of hexane and filtration gave N-[2-(4-benzyloxyphenyl)-1-methylethyl]-2-hydroxy-2-(3-chlorophenyl)ethanamine of analytical purity, mp 95°-99° C., as a 45:55 mixture of diastereoisomers.

Workup

  1. temperatureunder reflux for 90 minutes in an apparatus
  2. temperatureThe solution was cooled
  3. customthe solvent removed under reduced pressure
  4. dissolutionThe residue, dissolved in methanol (100 ml)
  5. temperaturewas cooled to less than 10° C.
  6. additiontreated portionwise with sodium borohydride (3.0 g) over 30 minutes
  7. stirringThe mixture was stirred for one hour at room temperature
  8. customthe solvent removed under reduced pressure
  9. dissolutionThe residue was dissolved in ethyl acetate
  10. washwashed with water
  11. dry with materialdried (magnesium sulphate)
  12. filtrationfiltered
  13. customevaporated to dryness
  14. customto give a solid

Sources & evidence

ORD record
ord-9521c15e98114e7abcc0c46f2263b93e
Source dataset
uspto-grants-1986_11
Patent number
US04622342

Reaction notes

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