Ethylene Glycol → Bosentan

HRID 1020777Notes

Reaction equation

HRID 1020777 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 (6.65 g), ethylene glycol (100 mL), tetrabutylammonium bromide (2.5 g), 4-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidin-4-yl]benzenesulfonamide (25 g) and dimethylsulphoxide (100 mL) were mixed and heated to 60° C. to 65° C. The reaction mixture was stirred for 12 hours to 14 hours at 60° C. to 65° C. The reaction mixture was cooled to 25° C. followed by the addition of dichloromethane (150 mL) and de-ionized water (250 mL). The pH of the mixture was adjusted to 2 to 3 with concentrated hydrochloric acid. The mixture was stirred for 10 minutes and the organic layer was separated. The aqueous layer was extracted with dichloromethane (50 mL). Both the organic layers were combined and washed with deionized water (125 mL). The dichloromethane was recovered and dried under vacuum at 40° C. to 50° C. to obtain the title compound.

Workup

  1. temperatureheated to 60° C. to 65° C
  2. stirringThe mixture was stirred for 10 minutes
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with dichloromethane (50 mL)
  5. washwashed with deionized water (125 mL)
  6. customThe dichloromethane was recovered
  7. customdried under vacuum at 40° C. to 50° C.

Sources & evidence

ORD record
ord-c0bd9f2d33784217b29a9b1af2470b03
Source dataset
uspto-grants-2014_05
Patent number
US08716477B2

Reaction notes

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