Methanol → 4-{2-[2-(2-Methoxyphenoxy)ethylamino]-2-methylethyl}-2-(methylthio)anisole

HRID 1614743Notes

Reaction equation

HRID 1614743 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](=O)[CH3:11])=[CH:5][C:4]=1[S:13][CH3:14].CO[CH:17]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:18][NH2:19].[BH4-].[Na+].[CH3:29][OH:30]>>[CH3:29][O:30][C:26]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:20][CH2:17][CH2:18][NH:19][CH:10]([CH3:11])[CH2:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([S:13][CH3:14])[CH:5]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 131788873-Methylthio-4-methoxyphenylacetoneHCID 534073742-Methoxyphenoxyethylamine

Product 1

HCID 131788884-{2-[2-(2-Methoxyphenoxy)ethylamino]-2-methylethyl}-2-(methylthio)anisole

Procedure

A mixture of 8.4 g of 4-methoxy-3-methylthiophenylacetone, 6.7 g of 2-methoxyphenoxyethylamine, and 150 ml of methanol was refluxed for 2 hours. The reaction mixture was cooled to a temperature below 10° C. and after adding 2.5 g of sodium borohydride to the reaction mixture with stirring at temperatures below 10° C., the mixture was further stirred for 3 hours at room temperature. Then, the solvent was distilled off under reduced pressure and after adding water to the residue, the product was extracted with ethyl acetate. The extract was washed with water, dried by anhydrous magnesium sulfate, and then the solvent was distilled off to provide an oily product. The product was purified by a silica gel column chromatography (eluate: chloroform) to provide 8.5 g of 4-{2-[2-(2-methoxyphenoxy)ethylamino]-2-methylethyl}-2-(methylthio)anisole. The product (750 mg) was dissolved in 10 ml of methanol and after adding thereto a solution of 90 mg of anhydrous oxalic acid dissolved in 1 ml of methanol, the mixture was allowed to stand overnight at room temperature. The crystals thus formed were recovered by filtration and recrystallized from ethanol to provide 600 mg of 4-{2-[2-(2-methoxyphenoxy)ethylamino]-2-methylethyl}-2-(methylthio)anisole oxalate having a melting point of 173°-174° C.

Workup

  1. temperaturewas refluxed for 2 hours
  2. temperatureThe reaction mixture was cooled to a temperature below 10° C.
  3. stirringthe mixture was further stirred for 3 hours at room temperature
  4. distillationThen, the solvent was distilled off under reduced pressure
  5. additionafter adding water to the residue
  6. extractionthe product was extracted with ethyl acetate
  7. washThe extract was washed with water
  8. dry with materialdried by anhydrous magnesium sulfate
  9. distillationthe solvent was distilled off
  10. customto provide an oily product
  11. customThe product was purified by a silica gel column chromatography (eluate: chloroform)

Sources & evidence

ORD record
ord-45d64a5c258c4c52a65adee374a990b9
Source dataset
uspto-grants-1993_03
Patent number
US05198587

Reaction notes

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