Dimethyl Sulfide → Tapentadol

HRID 534702Notes

Reaction equation

HRID 534702 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]([C@H:9]([CH2:16][CH3:17])[C@@H:10]([CH3:15])[CH2:11][N:12]([CH3:14])[CH3:13])[CH:6]=[CH:7][CH:8]=1.CS(O)(=O)=O.CSC>>[CH3:14][N:12]([CH3:13])[CH2:11][C@H:10]([CH3:15])[C@H:9]([C:5]1[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=1)[CH2:16][CH3:17]

Participants

4

Reactant 3

HCID 1068Dimethyl SulfideHCID 6395Methanesulfonic AcidHCID 112533283(3-Methoxyphenyl)-N,N,2-trimethyl pentane-1-amine, (2R,3R)-

Product 1

HCID 9838022Tapentadol

Conditions

Temperature
5 °C

Procedure

Accordingly the compound (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of Formula-VII was taken in pre cooled methanesulfonic acid and stirred at 0-10° C. Charged dimethyl sulfide to the reaction solution and raised the temperature of the reaction to 55-60° C. Maintained the reaction at 55-60° C. for 2-3 hours and cooled the reaction to 20-30° C. Quenched the reaction mass in ice cold water and extracted the reaction solution with toluene. Separated the aqueous layer and adjusted the pH to 9-10 with dilute aqueous sodium hydroxide solution. Extracted the aqueous layer with toluene and separated the toluene layer. Concentrated the solvent under reduced pressure to isolate the compound 3-[(2R,3R)-1-(dimethylamino)-2-methylpentan-3-yl]phenol of Formula-I.

Workup

  1. customthe temperature of the reaction to 55-60° C
  2. temperatureMaintained
  3. customthe reaction at 55-60° C. for 2-3 hours
  4. temperaturecooled
  5. customthe reaction to 20-30° C
  6. customQuenched the reaction mass in ice cold water
  7. extractionextracted the reaction solution with toluene
  8. customSeparated the aqueous layer
  9. extractionExtracted the aqueous layer with toluene
  10. customseparated the toluene layer
  11. concentrationConcentrated the solvent under reduced pressure

Sources & evidence

ORD record
ord-e6c943e7db9242cfb8ce9667c7d8b705
Source dataset
uspto-grants-2014_10
Patent number
US08853456B2

Reaction notes

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