Dimethylformamide → 5-Chloro-N-(chloroacetyl)-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide

HRID 421572Notes

Reaction equation

HRID 421572 reaction equation
[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:9][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.CN(C=O)C.[H-].[Na+].[Cl:37][CH2:38][C:39](Cl)=[O:40]>O>[Cl:1][C:2]1[S:6][C:5]([C:7]([N:9]([C:39](=[O:40])[CH2:38][Cl:37])[CH2:10][C@@H:11]2[O:15][C:14](=[O:16])[N:13]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][C:24]4=[O:29])=[CH:21][CH:22]=3)[CH2:12]2)=[O:8])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6577Chloroacetyl chlorideHCID 24758Sodium hydrideHCID 9875401Rivaroxaban2×

Product 1

HCID 581370315-Chloro-N-(chloroacetyl)-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1 g (2.3 mmol) of 5-chloro-N-({(5S)-2-oxo-3-[4-(3-oxomorpholin-4-yl)phenyl]-1,3-oxazolidin-5-yl}methyl)thiophene-2-carboxamide [compound (A)] is dissolved in 170 ml of abs. DMF under argon. 110 mg (4.6 mmol) of sodium hydride are added, and the mixture is stirred at RT for 20 min. Then 3.5 g (31 mmol) of chloroacetyl chloride are added, keeping the reaction temperature at RT. After 30 min, 25 ml of water are added while cooling, and the mixture is left to stand at RT for two days. The solvent is then removed in vacuo, during which the temperature should not rise above +25° C. The residue is taken up in 500 ml of dichloromethane and extracted five times with 200 ml of water. The organic phase is dried over magnesium sulphate, filtered and concentrated to a volume of about 50 ml. While stirring, 200 ml of diethyl ether are added, and the precipitate (mostly unreacted starting material) is then filtered off. The mother liquor is concentrated and the residue is purified by flash chromatography on silica gel with toluene/ethanol 10:1 as eluent. The appropriate fractions are combined, and the solvent is removed. The residue is lyophilized from dioxane.

Workup

  1. customat RT
  2. waitAfter 30 min
  3. temperaturewhile cooling
  4. waitthe mixture is left
  5. waitto stand at RT for two days
  6. customThe solvent is then removed in vacuo, during which the temperature should not
  7. customrise above +25° C
  8. extractionextracted five times with 200 ml of water
  9. dry with materialThe organic phase is dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated to a volume of about 50 ml
  12. stirringWhile stirring
  13. addition200 ml of diethyl ether are added
  14. filtrationthe precipitate (mostly unreacted starting material) is then filtered off
  15. concentrationThe mother liquor is concentrated
  16. customthe residue is purified by flash chromatography on silica gel with toluene/ethanol 10:1 as eluent
  17. customthe solvent is removed

Sources & evidence

ORD record
ord-3d72f88f120449218fcec81a360dbce3
Source dataset
uspto-grants-2012_01
Patent number
US08101601B2

Reaction notes

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