1,1'-Carbonyldiimidazole → Rivaroxaban

Participants

Reaction Conditions

Reaction Steps

Under an atmosphere of nitrogen to a suspension of 14.85 g of 5-chlorothiophen-2-carboxylic acid-{(R)-2-hydroxy-3-[4-(3-oxomorpholin-4-yl)phenylamino]propyl}amide (MW=409.89; 1 eq.) in 145 mL toluene and 22 mL N-methylpyrrolidone were added 7.13 g (MW=162.15; 1.2 eq.) of 1,1′-carbonyldiimidazol. The reaction mixture was heated to 80° C. After stirring for 30 minutes the mixture was heated to 110° C. and stirred at this temperature for 2 hours. Then the mixture was cooled to 22° C. After stirring for 1 hour at ambient temperature the product was isolated by filtration and washed with 60 mL of toluene and 60 mL of water. The wet product was dried at 30° C. in vacuo to yield 15.99 g (MW=435.89; 1.013 eq.) of the title compound (90% of theory).

Provenance & Evidence