Dichloromethane → tert-Butyl(3aS,6S,7aR)-6-(dimethylcarbamoyl)-2,2-dioxohexahydro-2,1,3-benzothiadiazole-1(3H)-carboxylate

HRID 64047Notes

Reaction equation

HRID 64047 reaction equation
C(Cl)Cl.[CH2:4]([N:6]([CH2:9]C)[CH2:7][CH3:8])C.CN(C)C([C@@H:15]1[CH2:20][C@@H:19]([NH:21][S:22]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:24])=[O:23])[C@H:18](O)[CH2:17]C1)=O.CS(Cl)(=O)=[O:37]>O>[CH3:9][N:6]([CH3:4])[C:7]([C@@H:8]1[CH2:15][C@H:20]2[N:25]([C:26]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:32])[S:22](=[O:24])(=[O:23])[NH:21][C@H:19]2[CH2:18][CH2:17]1)=[O:37]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 118671017Edoxaban Impurity 158

Product 1

HCID 118661248tert-Butyl(3aS,6S,7aR)-6-(dimethylcarbamoyl)-2,2-dioxohexahydro-2,1,3-benzothiadiazole-1(3H)-carboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Methylene chloride (200 ml) and triethylamine (18.5 ml) were added to tert-butyl {[(1R,2R,5S)-5-(dimethylcarbamoyl)-2-hydroxycyclohexyl]sulfamoyl}carbamate (20 g), and the obtained solution was then cooled to approximately 0° C. Methanesulfonyl chloride (5.2 ml) was added dropwise to the reaction solution, and the obtained mixture was then stirred for approximately 1 hour. Thereafter, water (100 ml) was added to the reaction mixture, and the organic layer was then separated. The solvent was distilled off from the organic layer under reduced pressure. To the residue, acetonitrile (200 ml) and triethylamine (15.4 ml) were added, and the obtained mixture was then heated to approximately 90° C., followed by stirring the mixture for approximately 2 hours. Thereafter, the reaction mixture was cooled to room temperature, 10% saline (100 ml) was then added to the mixture, and the organic layer was then separated. The aqueous layer was extracted with ethyl acetate (100 ml) again. The gathered organic layers were concentrated, and the obtained residue was purified by silica gel column chromatography to obtain the title compound (14.02 g, yield: 74%) in the form of powder.

Workup

  1. customthe organic layer was then separated
  2. distillationThe solvent was distilled off from the organic layer under reduced pressure
  3. additionTo the residue, acetonitrile (200 ml) and triethylamine (15.4 ml) were added
  4. temperaturethe obtained mixture was then heated to approximately 90° C.
  5. stirringby stirring the mixture for approximately 2 hours
  6. temperatureThereafter, the reaction mixture was cooled to room temperature
  7. addition10% saline (100 ml) was then added to the mixture
  8. customthe organic layer was then separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (100 ml) again
  10. concentrationThe gathered organic layers were concentrated
  11. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a106b1f33c724ab497ac1f60aaf6a63d
Source dataset
uspto-grants-2016_09
Patent number
US09447118B2

Reaction notes

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