Ethylene Glycol → Bosentan

HRID 1020775

Reaction equation

HRID 1020775 reaction equation
[OH-].[Na+].[CH2:3]([OH:6])[CH2:4][OH:5].[C:7]([C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][C:21]2[C:26]([O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[C:25](Cl)[N:24]=[C:23]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:22]=2)(=[O:19])=[O:18])=[CH:13][CH:12]=1)([CH3:10])([CH3:9])[CH3:8].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O.ClCCl.CS(C)=O>[CH3:8][C:7]([C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:20][C:21]2[C:26]([O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[C:25]([O:5][CH2:4][CH2:3][OH:6])[N:24]=[C:23]([C:37]3[N:42]=[CH:41][CH:40]=[CH:39][N:38]=3)[N:22]=2)(=[O:19])=[O:18])=[CH:13][CH:12]=1)([CH3:10])[CH3:9]

Participants

9

Reactant 4

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 111351604-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

Product 1

HCID 104865Bosentan

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

Sodium hydroxide (26.66 g), ethylene glycol (400 mL), tetrabutylammonium bromide (10 g), 4-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidin-4-yl]benzenesulfonamide (100 g) and dimethylsulphoxide (400 mL) were mixed together at 25° C. The reaction mixture was heated to 60° C. to 65° C. and the mixture was stirred for 12-14 hours at 60° C. to 65° C. The reaction mixture was cooled to 25° C. followed by the addition of dichloromethane (600 mL) and de-ionized water (1000 mL). The pH of the mixture was adjusted to 2 to 3 with concentrated hydrochloric acid and the mixture was stirred for 10 minutes. The organic layer of the reaction mixture was separated. The aqueous layer was extracted with dichloromethane (200 mL). Both the organic layers were combined, washed with de-ionized water (500 mL) and the solvent was recovered. The residue was dried under vacuum at 40° C. to 50° C. to obtain bosentan.

Workup

  1. temperatureThe reaction mixture was heated to 60° C. to 65° C.
  2. stirringthe mixture was stirred for 10 minutes
  3. customThe organic layer of the reaction mixture was separated
  4. extractionThe aqueous layer was extracted with dichloromethane (200 mL)
  5. washwashed with de-ionized water (500 mL)
  6. customthe solvent was recovered
  7. customThe residue was dried under vacuum at 40° C. to 50° C.

Sources & evidence

ORD record
ord-8bfb742a3241403aaf99ad34d32767bb
Source dataset
uspto-grants-2014_05
Patent number
US08716477B2

Linked notes

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