Ethylene Glycol → Bosentan

HRID 1183781Notes

Reaction equation

HRID 1183781 reaction equation
[CH2:1]([OH:4])[CH2:2][OH:3].[OH-].[Na+].[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].C(O)(=O)C(C(C(O)=O)O)O>O1CCCC1.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:3][CH2:2][CH2:1][OH:4])[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

7

Reactant 4

HCID 174Ethylene GlycolHCID 8752,3-Dihydroxybutanedioic AcidHCID 14798Sodium HydroxideHCID 111351604-Tert-butyl-n-(6-chloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide

Product 1

HCID 104865BosentanYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethylene glycol (315.29 g, 107 eq) was mixed in tetrahydrofuran (175 ml, 7 vol) and sodium hydroxide (19.01 g, 10 eq) was added. The mixture was heated to 50° C. for 30 minutes or until the solution became clear. To the clear solution was added 4-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-pyrimidin-4-yl]-benzenesulfonamide (25 g, 1 eq) at 50° C. and stirred at 65° C. for 12 hours. The tetrahydrofuran was distilled out under vacuum at 210-220 mbar pressure at 35° C. The resulting solution was cooled to 10° C., a solution of tartaric acid (35.65 g, 5 eq) in water (100 ml, 4 vol) was added and stirred for 1.5 hours at the same temperature. The resultant solid was filtered, washed with a mixture of isopropyl alcohol (100 ml, 4 vol), ethanol (50 ml, 2 vol) and water (200 ml, 8 vol), and dried under vacuum at 60° C. to obtain the product as an off-white solid.

Workup

  1. distillationThe tetrahydrofuran was distilled out under vacuum at 210-220 mbar pressure at 35° C
  2. temperatureThe resulting solution was cooled to 10° C.
  3. stirringstirred for 1.5 hours at the same temperature
  4. filtrationThe resultant solid was filtered
  5. washwashed with a mixture of isopropyl alcohol (100 ml, 4 vol), ethanol (50 ml, 2 vol) and water (200 ml, 8 vol)
  6. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-4c811043c9f8467ea7b2c5b0f941c422
Source dataset
uspto-grants-2014_03
Patent number
US08664390B2

Reaction notes

Loading…