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Chemical synthesis study demonstrates efficient total synthesis of ruxolitinib using mechanochemistry and microwave heating, suggesting a greener route for complex drug manufacturing.
Syntheses of highly structurally complex compounds such as pharmaceuticals belong among the most demanding from a sustainability point of view. Herein, we present the total synthesis of an important pharmaceutical, ruxolitinib, through the strategic application of mechanochemistry, microwave irradiation, and green solvents. Mechanochemistry proved useful for the Wittig reaction, ester reduction, and alcohol oxidation, leading to short reaction times and high yields. Moreover, the key step of the synthesis, the asymmetric organocatalytic aza-Michael addition, can also be carried out under mechanochemical conditions, affording an aza-Michael adduct with high enantiomeric purity. Alternatively, this step can be augmented by using green solvent alternatives. Final functional group transformation and deprotection benefited from microwave irradiation.
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Mravíková et al. (2026) studied this question.
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