反应详情

Illustrative embodiments of the present invention provide a process for preparing APO-II comprising: i. mixing Warfarin acid in isopropanol thereby forming a Warfarin mixture; ii. adding to the Warfarin mixture a potassium base selected from either ii-i) KOH, K2CO3, KHCO3, K3PO4, KOH in water, K2CO3 in water, KHCO3 in water, K3PO4 in water, KOH in ROH, K2CO3 in ROH, KHCO3 in ROH, K3PO4 in ROH, and mixtures thereof, wherein R is selected from the group consisting of H and C1-C4 alkyl, or ii-ii) KOH, K2CO3, KHCO3, K3PO4, KH, KNH2, potassium bis(trimethylsilyl)amide, potassium diisopropylamide and mixtures thereof, thereby forming a potassium Warfarin mixture; iii. heating the potassium Warfarin mixture to a temperature in a range of from about 45° C. to about 80° C. thereby forming a first solution; iv. maintaining the first solution at a pH in a range of from about 7.0 to about 10.0 thereby forming a Warfarin potassium isopropanol solution; v. distilling the Warfarin potassium isopropanol solution thereby forming a concentrated Warfarin potassium isopropanol solution; vi. adding additional isopropanol to the concentrated Warfarin potassium isopropanol solution and distilling further to remove water thereby forming a distilled Warfarin potassium isopropanol solution; vii. distilling the distilled Warfarin potassium isopropanol solution to dryness or near-dryness thereby forming a Warfarin potassium residue; viii. dissolving the Warfarin potassium residue in ethyl acetate thereby forming a Warfarin potassium ethyl acetate solution; ix. stirring the Warfarin potassium ethyl acetate solution at a temperature in a range of from about 5° C. to about 50° C. until precipitation occurs thereby forming a precipitate; and x. isolating the precipitate thereby isolating APO-II.