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N-(4-Methoxyphenyl)-3-oxobutanamide is an intermediate in the synthesis of Tafenoquine-d3 Succinate is the labelled analog of Tatenoquine (T004760), a new 8-aminoquinoline with an improved therapeutic index and safety profile as compared to primaquine (P733500).Tafenoquine has the potential to become a widely used drug in the prevention and treatment of malaria infection and could replace some currently used drugs as resistant strains of Plasmodium species increase.

The Journal of Organic Chemistry, 11, p. 803, 1946 DOI: 10.1021/jo01176a024

GENERAL STEPS: In a 100 mL round-bottomed flask, ethyl acetoacetate (0.03 mol) was added to a stirring solution of p-aminoanisole (0.01 mol) dissolved in 10 mL of PEG-300. The reaction mixture was refluxed at 120 °C for 1.5-2 hours. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was cooled to room temperature and subsequently extracted with cold ether (3 x 10 mL). The organic phases were combined and purified by column chromatography (eluent: hexane solution of 10-25% ethyl acetate) to afford the target product N-(4-methoxyphenyl)-3-oxobutylamide (3a-p). The structure of the final product was confirmed by methods reported in the literature.

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