Chlorotrimethylsilane → Tapentadol Hydrochloride

HRID 875299Notes

Reaction equation

HRID 875299 reaction equation
[CH3:1][CH2:2][C@H:3]([C@H:11]([CH2:13][N:14]([CH3:16])[CH3:15])[CH3:12])[C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([OH:10])[CH:9]=1.CC(=O)CC.C[Si](C)(C)[Cl:24]>O>[CH3:1][CH2:2][C@H:3]([C@H:11]([CH2:13][N:14]([CH3:16])[CH3:15])[CH3:12])[C:4]1[CH:5]=[CH:6][CH:7]=[C:8]([OH:10])[CH:9]=1.[ClH:24]

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 6569Methyl Ethyl KetoneHCID 9838022Tapentadol

Product 1

HCID 9838021Tapentadol HydrochlorideYield 97.78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
22.5 °C

Procedure

Tapentadol free base (2.1 g) was added to 2-butanone (32 ml), the mixture was heated to reflux and followed by the addition of water (0.22 ml) and trimethylchlorosilane (1.6 ml) at the same temperature and then maintaining for 1 hour. The resulting mass was cooled at 20-25° C. The resulting solid was filtered, the product was washed with pre-cooled 2-butanone (4 ml) and then the solid was dried at 25° C. for 3 hours to produce 1.8 g of tapentadol hydrochloride salt (Purity by HPLC: 97.78%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. temperaturemaintaining for 1 hour
  4. filtrationThe resulting solid was filtered
  5. washthe product was washed with pre-cooled 2-butanone (4 ml)
  6. customthe solid was dried at 25° C. for 3 hours

Sources & evidence

ORD record
ord-4fbfd99123684f6a876ec27414c202b0
Source dataset
uspto-grants-2015_03
Patent number
US08981154B2

Reaction notes

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