Water → Tapentadol

HRID 1094920Notes

Reaction equation

HRID 1094920 reaction equation
CS(O)(=O)=O.N[C@H](C(O)=O)CCSC.C[O:16][C:17]1[CH:18]=[C:19]([C@H:23]([CH2:30][CH3:31])[C@@H:24]([CH3:29])[CH2:25][N:26]([CH3:28])[CH3:27])[CH:20]=[CH:21][CH:22]=1.O>CC1CCCCC1>[CH3:28][N:26]([CH3:27])[CH2:25][C@H:24]([CH3:29])[C@H:23]([C:19]1[CH:18]=[C:17]([OH:16])[CH:22]=[CH:21][CH:20]=1)[CH2:30][CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 6137L-MethionineHCID 6395Methanesulfonic AcidHCID 112533283(3-Methoxyphenyl)-N,N,2-trimethyl pentane-1-amine, (2R,3R)-

Product 1

HCID 9838022TapentadolYield 89.5%

Reagents, catalysts & solvents 1

HCID 7962MethylcyclohexaneSolvent2×

Conditions

Temperature
82 °C

Procedure

18.9 kg of methanesulfonic acid and 2458 g D,L methionine were placed in methyl cyclohexane and then 3192 g (2R,3R)-[3-(3-methoxy-phenyl)-2-methyl-pentyl]-dimethylamine were added and the mixture was stirred at 82° C. for 18 hours. Subsequently, dilution was carried out with 10.3 l water at a maximum of 80° C. and 9 l methyl cyclohexane were added. At a maximum of 42° C., 17.3 l ammoniac were added until the pH was 8.8. A phase separation took place at 45° C. and 3.2 g (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol were added to the organic phase at 40° C. and stirred for 1 hour at 36° C. Subsequently, after cooling slowly to 5° C. and a further hour of stirring, the precipitate which formed was extracted by suction, washed with 12 l methyl cyclohexane and dried in a drying chamber. 2685 g (89.5%) (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol were obtained in modification B.

Workup

  1. additionwere added
  2. additionAt a maximum of 42° C., 17.3 l ammoniac were added until the pH was 8.8
  3. customA phase separation
  4. customat 45° C.
  5. addition3.2 g (1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol were added to the organic phase at 40° C.
  6. stirringstirred for 1 hour at 36° C
  7. temperatureSubsequently, after cooling slowly to 5° C. and a further hour
  8. stirringof stirring
  9. customthe precipitate which formed
  10. extractionwas extracted by suction
  11. washwashed with 12 l methyl cyclohexane
  12. customdried in a drying chamber

Sources & evidence

ORD record
ord-3a1c836cbeee4b5a93f69b14b95b1075
Source dataset
uspto-grants-2012_03
Patent number
US08134032B2

Reaction notes

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