A systematic study towards the synthesis, isolation and recrystallization of Atovaquone, an antimalarial drug: a sustainable synthetic pathway
Keywords:2-[trans-4-(4-chlorophenyl) cyclohexyl]-3-hydroxy-1, 4-naphthoquinone(Atovaquone), reaction optimization, isolation, recrystallization
In the present work, studies were conducted towards the synthesis of Atovaquone 5 with systematic reaction and recrystallization condition optimization to isolate 5 in high yield with better purity. Synthesis of 5 was done by the hydrolysis of 2-[trans-4-(4-chlorophenyl) cyclohexyl]-3-chloro-1,4-naphthoquinone 4, which was isolated by the decarboxylative condensation of trans-4-(4-chlorophenyl) cyclohexane carboxylic acid 3 with naphthoquinone moiety. After the hydrolysis of 4, isolation of crude 5 was done by the use of acetic acid instead of dilute hydrochloric acid, product 5 was isolated in good purity with very less polar impurities. The use of a large volume of solvent becomes a bottleneck for the commercial synthesis of 5. Our efforts towards optimization of hydrolysis reaction and recrystallization of 5 with the use of small volume of solvent combination had made the process to be more cost effective and commercially viable for large scale manufacturing.
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