Hydrochloric Acid → Bosentan hydrate

HRID 2280511Notes

Reaction equation

HRID 2280511 reaction equation
[CH3:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[C:16]([O:31][C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:37]=3[O:38][CH3:39])=[C:17]([O:27][CH2:28][CH2:29][OH:30])[N:18]=[C:19]([C:21]3[N:22]=[CH:23][CH:24]=[CH:25][N:26]=3)[N:20]=2)(=[O:13])=[O:12])=[CH:9][CH:10]=1)([CH3:4])[CH3:3].ClCCl.Cl>O.C(O)C>[CH3:4][C:2]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[N:20]=[C:19]([C:21]3[N:22]=[CH:23][CH:24]=[CH:25][N:26]=3)[N:18]=[C:17]([O:27][CH2:28][CH2:29][OH:30])[C:16]=2[O:31][C:32]2[C:37]([O:38][CH3:39])=[CH:36][CH:35]=[CH:34][CH:33]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:1])[CH3:3].[OH2:12]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 104865Bosentan

Product 1

HCID 185462Bosentan hydrateYield 193.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To the pure ammonium salt of Bosentan (60 gm), dichloromethane (180 ml) and water (180 ml) were added and the pH of the reaction mixture was adjusted to 5 to 6 using concentrated hydrochloric acid. The reaction mixture was stirred for 30 minutes. The dichloromethane layer was separated and it was washed with water (180 ml). The dichloromethane layer was subjected to evaporation under reduced pressure to obtain syrup. To this syrup, ethanol (120 ml) was added and the mixture was heated to 55° C. to 60° C. to obtain clear solution. Water (120 ml) was slowly added to the clear solution and was stirred for 30 minutes at 55° C. to 60° C. The reaction mixture was cooled to 25° C. to 30° C. and the mixture was stirred for 30 to 45 minutes at 25° C. to 30° C. The solid obtained was filtered and was dried at 40° C. for 2 to 4 hours, to yield Bosentan monohydrate (60 gm).

Workup

  1. customThe dichloromethane layer was separated
  2. washit was washed with water (180 ml)
  3. customThe dichloromethane layer was subjected to evaporation under reduced pressure
  4. customto obtain syrup
  5. temperaturethe mixture was heated to 55° C. to 60° C.
  6. customto obtain clear solution
  7. stirringwas stirred for 30 minutes at 55° C. to 60° C
  8. temperatureThe reaction mixture was cooled to 25° C. to 30° C.
  9. stirringthe mixture was stirred for 30 to 45 minutes at 25° C. to 30° C
  10. customThe solid obtained
  11. filtrationwas filtered
  12. customwas dried at 40° C. for 2 to 4 hours

Sources & evidence

ORD record
ord-e97cac8364e2444892ce260c567f17b2
Source dataset
uspto-grants-2015_09
Patent number
US09139537B2

Reaction notes

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