Acetone → Topotecan Acetate

Participants

Reaction Conditions

Reaction Steps

0.3 Kg of 10-hydroxy camptothecin (Formula IV) prepared according to Example-1 was suspended in 6 L of acetic acid and stirred for 5 minutes. The obtained solution was charged into a reactor and stirred for 20 minutes. 0.51 L of a 40% aqueous solution of dimethyl amine and 0.078 L of a 37% of aqueous solution of formaldehyde were charged into the reactor, the temperature raised to 45.3° C. and the reaction mixture stirred for 2 hours at 45.3° C. The reaction solution was allowed to cool to 34.8° C. and then cooled to 27.5° C. 42 L of acetone was charged into above reaction solution and stirred for 1 hour at 27.5° C. for complete precipitation. The formed solid was filtered and the reactor rinsed with 1.5 L of acetone. The wet solid was washed with the rinsing and then washed with 0.3 L of 1-propanol. The resultant solid was suction dried for 20 minutes and then dried for 5 hours at 52° C. under a vacuum of 690 mm Hg to afford 330 g of title compound having a purity by HPLC of about 98.9%.

Provenance & Evidence