Ethylene Glycol → Bosentan

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence