Dichloromethane → Rivaroxaban

HRID 1054157Notes

Reaction equation

HRID 1054157 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([N:9](C=O)[CH2:10][C@@H:11]2[O:15][C:14](=[O:16])[N:13]([C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C:24]4=[O:29])=[CH:19][CH:18]=3)[CH2:12]2)=[O:8])=[CH:4][CH:3]=1.ClCCl.CS(O)(=O)=O>CO>[CH:19]1[C:20]([N:23]2[C:24](=[O:29])[CH2:25][O:26][CH2:27][CH2:28]2)=[CH:21][CH:22]=[C:17]([N:13]2[C:14](=[O:16])[O:15][C@@H:11]([CH2:10][NH:9][C:7]([C:5]3[S:6][C:2]([Cl:1])=[CH:3][CH:4]=3)=[O:8])[CH2:12]2)[CH:18]=1

Participants

5

Reactant 3

HCID 6344Dichloromethane2×HCID 6395Methanesulfonic AcidHCID 76072855HCID 76072855, compound

Product 1

HCID 9875401Rivaroxaban

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

In four neck round bottom flask charge 5-chloro-N-formyl-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (120 g), dichloromethane(2400 ml) and 70% methanesulphonic acid (120 ml) at 25-30° C. Obtained reaction mixture is heated to reflux for 4 to 5 h. After completion of reaction, concentrate reaction mass under reduced pressure to obtain residue. Added Dichloromethane (120 ml) and slowly added Methanol (600 ml) to the residue. The precipitated solid is filtered off and washed by methanol (240 ml)

Workup

  1. customObtained
  2. customreaction mixture
  3. temperatureis heated
  4. temperatureto reflux for 4 to 5 h
  5. customAfter completion of reaction
  6. concentrationconcentrate
  7. customreaction mass under reduced pressure
  8. customto obtain residue
  9. filtrationThe precipitated solid is filtered off
  10. washwashed by methanol (240 ml)

Sources & evidence

ORD record
ord-5327948ef41e4628b8fd5efe3cc5caf7
Source dataset
uspto-grants-2016_07
Patent number
US09394292B2

Reaction notes

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