Ethanol → Edoxaban tosylate monohydrate

HRID 2104460Notes

Reaction equation

HRID 2104460 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:37])[C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:15][C@H:14]2[NH:24][C:25]([C:27]2[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=2)=[O:26])=[O:11])=[N:6][CH:7]=1.C(O)C.[C:41]1([CH3:51])[CH:46]=[CH:45][C:44]([S:47]([OH:50])(=[O:49])=[O:48])=[CH:43][CH:42]=1>C(Cl)Cl>[OH2:11].[C:41]1([CH3:51])[CH:42]=[CH:43][C:44]([S:47]([OH:50])(=[O:48])=[O:49])=[CH:45][CH:46]=1.[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:37])[C:10]([NH:12][C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([N:21]([CH3:23])[CH3:22])=[O:20])[CH2:15][C@H:14]2[NH:24][C:25]([C:27]2[S:28][C:29]3[CH2:30][N:31]([CH3:36])[CH2:32][CH2:33][C:34]=3[N:35]=2)=[O:26])=[O:11])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 6101p-Toluenesulfonic acidHCID 10280735Edoxaban

Product 1

HCID 25022378Edoxaban tosylate monohydrate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

The compound (6.2 g) obtained in Example 310 is dissolved in methylene chloride (120 mL), a 1 mol/L ethanol solution (11.28 mL) of p-toluenesulfonic acid was added to the solution, and the solvent was distilled away. Ethanol (95 mL) containing 15% water was added to the residue, and the mixture was stirred at 60° C. to dissolve it. The solution was then cooled to room temperature and stirred for a day. Crystals precipitated were collected by filtration, washed with ethanol and dried at room temperature for 2 hours under reduced pressure to give the title compound (7.4 g).

Workup

  1. distillationthe solvent was distilled away
  2. additionEthanol (95 mL) containing 15% water
  3. additionwas added to the residue
  4. dissolutionto dissolve it
  5. temperatureThe solution was then cooled to room temperature
  6. stirringstirred for a day
  7. customCrystals precipitated
  8. filtrationwere collected by filtration
  9. washwashed with ethanol
  10. customdried at room temperature for 2 hours under reduced pressure

Sources & evidence

ORD record
ord-635d71a3f7344709bfcf9a15398cc6d6
Source dataset
uspto-grants-2009_08
Patent number
US07576135B2

Reaction notes

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