Ethylene Glycol → Bosentan

HRID 1020783Notes

Reaction equation

HRID 1020783 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>[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

8

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 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of sodium hydroxide (2.66 g), ethylene glycol (60 mL), tetrabutylammonium bromide (1 g) and 4-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidin-4-yl]benzenesulfonamide (10 g) was heated to 95° C. to 100° C. and the reaction mixture was stirred for 4 hours at 95° C. to 100° C. The mixture was cooled to 25° C. followed by the addition of dichloromethane (40 mL) and de-ionized water (180 mL). The pH of the reaction mixture was adjusted to 2 to 3 with concentrated hydrochloric acid. The reaction mixture was stirred for 10 minutes and the organic layer was separated. The aqueous layer was extracted with dichloromethane (10 mL). Both the organic layers were combined and washed with de-ionized water (50 mL). The dichloromethane was recovered under vacuum at 40° C. to 50° C. to obtain the title compound.

Workup

  1. temperaturewas heated to 95° C. to 100° C.
  2. stirringThe reaction mixture was stirred for 10 minutes
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with dichloromethane (10 mL)
  5. washwashed with de-ionized water (50 mL)
  6. customThe dichloromethane was recovered under vacuum at 40° C. to 50° C.

Sources & evidence

ORD record
ord-3ef5eb77a61a4c66abb464af0c434e84
Source dataset
uspto-grants-2014_05
Patent number
US08716477B2

Reaction notes

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