Dimethylformamide → HCID 59578782, compound

HRID 1809116Notes

Reaction equation

HRID 1809116 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][CH2:39][CH2:40][C:41](Cl)=[O:42]>O.C(OCC)(=O)C>[Cl:1][C:2]1[S:6][C:5]([C:7]([N:9]([C:41](=[O:42])[CH2:40][CH2:39][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

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 783704-Chlorobutyryl chlorideHCID 9875401Rivaroxaban2×

Product 1

HCID 59578782HCID 59578782, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

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 100 ml of abs. DMF under argon. 110 mg (4.6 mmol) of sodium hydride (98% strength) are added, and the mixture is stirred at RT for 20 min. Then 4.37 g (30.97 mmol) of chlorobutanoyl chloride are added, keeping the reaction temperature at RT. The reaction mixture is stirred at RT for 16 h and is then admixed with 25 ml of water added gradually with cooling. Subsequently, 300 ml of ethyl acetate are added and a further 50 ml of water. The phases are separated and the ethyl acetate phase is concentrated in vacuo. The residue is stirred up with ethyl acetate and filtered. The mother liquor is concentrated and the residue is purified by flash chromatography on silica gel with toluene/ethanol 5:1 as eluent. The appropriate fractions which contain the target compound and also those which contain a bis-acylated compound formed after enolization are combined and the solvent is removed. The residue is admixed with a saturated solution of hydrogen chloride in dichloromethane and stirred at RT overnight. This is followed by concentrating in vacuo and the residue is again purified by flash chromatography on silica gel with toluene/ethanol 6:1 as eluent. The appropriate fractions are concentrated and the residue is lyophilized from dioxane to obtain 94 mg (7.5% of theory) of the target compound.

Workup

  1. customat RT
  2. stirringThe reaction mixture is stirred at RT for 16 h
  3. additionadded gradually
  4. temperaturewith cooling
  5. customThe phases are separated
  6. concentrationthe ethyl acetate phase is concentrated in vacuo
  7. stirringThe residue is stirred up with ethyl acetate
  8. filtrationfiltered
  9. concentrationThe mother liquor is concentrated
  10. customthe residue is purified by flash chromatography on silica gel with toluene/ethanol 5:1 as eluent
  11. customformed after enolization
  12. customthe solvent is removed
  13. stirringstirred at RT overnight
  14. concentrationby concentrating in vacuo
  15. customthe residue is again purified by flash chromatography on silica gel with toluene/ethanol 6:1 as eluent
  16. concentrationThe appropriate fractions are concentrated
  17. customto obtain 94 mg (7.5% of theory) of the target compound

Sources & evidence

ORD record
ord-7cdc8c7f1ebb4305865f023f104f71e5
Source dataset
uspto-grants-2013_01
Patent number
US08362015B2

Reaction notes

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