Ethanol → Rivaroxaban

HRID 2199709Notes

Reaction equation

HRID 2199709 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]#[N:8])=[CH:4][CH:3]=1.N[CH2:10][C@@H:11]1[O:15][C:14](=[O:16])[N:13]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C:24]3=[O:29])=[CH:19][CH:18]=2)[CH2:12]1.C([OH:32])C>Cl>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:8][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:32])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 11346837(S)-4-(4-(5-(aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-oneHCID 122032655-Chloro-2-thiophenecarbonitrile

Product 1

HCID 9875401Rivaroxaban

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To a solution of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one hydrochloride (5.7 g) in ethanol (70 ml) added potassium carbonate (7.1 g) and the mixture was stirred 2 h at 25 to 30° C. then filtered to obtain 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one (free base). In another flask charged solution of 5-chlorothiophene-2-carbonitrile (2.9 g) under nitrogen in ethanolic HCl (12 ml) and stirred for 5 h at room temperature till white precipitate was obtained. Distilled under nitrogen to avoid from moisture and obtained residue added in solution of 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}morpholin-3-one. The mixture was stirred for 16 to 18 h at reflux temperature. Aq. ethanol (5 ml) was and mixture heated at reflux temperature for 10 to 12 h to obtain 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide (crud material) which is further purified by column Chromatography.

Workup

  1. customwas obtained
  2. distillationDistilled under nitrogen
  3. customobtained residue
  4. stirringThe mixture was stirred for 16 to 18 h
  5. temperatureat reflux temperature
  6. temperaturemixture heated
  7. temperatureat reflux temperature for 10 to 12 h

Sources & evidence

ORD record
ord-74fca71ae5334e19b7e81226503e72ba
Source dataset
uspto-grants-2016_06
Patent number
US09359341B2

Reaction notes

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