Water → N-[2-(4-(2-Hydroxyethoxy)phenyl)-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine

HRID 851171Notes

Reaction equation

HRID 851171 reaction equation
[C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14](=O)[CH3:15])=[CH:9][CH:8]=1)([O:3]C)=O.[OH:17][CH:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[F:27])[CH2:19][NH2:20].O>C1C=CC=CC=1>[OH:3][CH2:1][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([NH:20][CH2:19][CH:18]([OH:17])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[F:27])[CH3:15])=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 962WaterHCID 13851156Methyl 2-(4-(2-oxopropyl)phenoxy)acetateHCID 150671762-Amino-1-(2-fluorophenyl)ethan-1-ol

Product 1

HCID 13079624N-[2-(4-(2-Hydroxyethoxy)phenyl)-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of 1-(4-carbomethoxymethoxyphenyl)propan-2-one (2.22 g) and 2-hydroxy-2-(2-fluorophenyl)ethanamine (1.55 g) in benzene (100 ml) was boiled under reflux with azeotropic removal of water using a Dean and Stark trap, for 2 hours. The solution was cooled, evaporated to dryness, the residue dissolved in methanol and sodium borohydride (500 mg) added. After 30 minutes, the methanol was evaporated and the residue partitioned between ethyl acetate and water. The organic layer was dried (magnesium sulphate) and evaporated to leave an oil which was chromatographed on silica gel 60 eluting with 2% methanol/chloroform. N-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers.

Workup

  1. temperatureThe solution was cooled
  2. customevaporated to dryness
  3. dissolutionthe residue dissolved in methanol
  4. additionsodium borohydride (500 mg) added
  5. waitAfter 30 minutes
  6. customthe methanol was evaporated
  7. customthe residue partitioned between ethyl acetate and water
  8. dry with materialThe organic layer was dried (magnesium sulphate)
  9. customevaporated
  10. customto leave an oil which
  11. customwas chromatographed on silica gel 60 eluting with 2% methanol/chloroform
  12. customN-[2-(4-(2-hydroxyethoxy)phenyl-1-methylethyl]-2-hydroxy-2-(2-fluorophenyl)ethanamine (300 mg) crystallised from hexane, m.p. 80°-95°, as a 55:45 mixture of diastereoisomers

Sources & evidence

ORD record
ord-2339547bef55412f994753969116a060
Source dataset
uspto-grants-1983_05
Patent number
US04382958

Reaction notes

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