Ethanol → Edoxaban tosylate monohydrate

Participants

Reaction Conditions

Reaction Steps

TsOH.H2O (49.5 g) was added to a mixed solution of N1-(5-chloropyridin-2-yl)-N2-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide (150 g), ethanol (735 ml), and water (315 ml), and the mixture was heated to 70° C. The dissolved solution was filtered through a filter, and the filter was washed with 15% aqueous ethanol (300 ml) and ethanol (150 ml). Subsequently, a mixed solution of the filtered mother liquor and the washes was slowly cooled, and TsOH.H2O (7.8 g) and ethanol (2100 ml) were added thereto. After stirring at 10° C. for 1 hour, crystals were collected by filtration, to obtain 188.9 g of the title compound.

Provenance & Evidence