Itraconazole → Malic Acid

Participants

Reaction Steps

Co-crystals of itraconazole and malic acid were prepared. To prepare the L-malic acid co-crystal salt of cis-itraconazole, 100.4 mg of cis-itraconazole free base, 0.50 mL of THF, and a magnetic stir bar were charged into a screw cap vial. A solution of 191.3 mg of L(−)malic acid in 5.0 mL of THF was prepared. 0.50 mL of the L-malic acid solution was added to the vial containing cis-itraconazole and the solution was heated with a heat gun to dissolve. The solution was allowed to cool and was then seeded with <1 mg of the salt from cis-itraconazole-L-tartaric acid co-crystal. The cooled crystals were filtered in a centrifuge filter tube. The filter cake was broken-up and allowed to air-dry prior to analysis. (See FIGS. 18 and 19)

Provenance & Evidence