Water → HCID 118661229, compound

HRID 64043Notes

Reaction equation

HRID 64043 reaction equation
C(N(CC)CC)C.[CH3:8][N:9]([CH3:31])[C:10]([C@@H:12]1[CH2:17][C@@H:16]([NH:18][S:19]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])(=[O:21])=[O:20])[C@H:15]([OH:30])[CH2:14][CH2:13]1)=[O:11].[CH3:32][S:33](Cl)(=[O:35])=[O:34].O>C(#N)C>[CH3:32][S:33]([O:30][C@@H:15]1[CH2:14][CH2:13][C@H:12]([C:10](=[O:11])[N:9]([CH3:8])[CH3:31])[CH2:17][C@H:16]1[NH:18][S:19](=[O:20])(=[O:21])[NH:22][C:23]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:29])(=[O:35])=[O:34]

Participants

6

Reactant 4

HCID 962Water2×HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 118671017Edoxaban Impurity 158

Product 1

HCID 118661229HCID 118661229, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Acetonitrile (460 ml) and triethylamine (87.0 ml) were added to a solution of tert-butyl {[(1R,2R,5S)-5-(dimethylcarbamoyl)-2-hydroxycyclohexyl]sulfamoyl}carbamate (138.5 g) in acetonitrile (300 ml), and the obtained solution was then cooled to approximately 0° C. Methanesulfonyl chloride (38.5 ml) was added dropwise to the reaction solution, and the obtained mixture was then stirred for approximately 30 minutes. Thereafter, water (610 ml) was added to the reaction mixture, and the obtained mixture was stirred for approximately 30 minutes. Subsequently, water (930 ml) was added to the reaction mixture, and the obtained mixture was further stirred for approximately 3 hours. Thereafter, the precipitated solid was collected by filtration and was then washed with 27.5% aqueous acetonitrile (300 ml). The obtained solid was dried under reduced pressure to obtain the title compound (138.5 g, yield: 82%).

Workup

  1. stirringthe obtained mixture was stirred for approximately 30 minutes
  2. stirringthe obtained mixture was further stirred for approximately 3 hours
  3. filtrationThereafter, the precipitated solid was collected by filtration
  4. washwas then washed with 27.5% aqueous acetonitrile (300 ml)
  5. customThe obtained solid was dried under reduced pressure

Sources & evidence

ORD record
ord-c85d78b5ff584d8ab3fde5fac4789881
Source dataset
uspto-grants-2016_09
Patent number
US09447118B2

Reaction notes

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