651324-04-8Relevant articles and documents
Preparation method of oseltamivir phosphate key intermediate hydrochloride
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Paragraph 0023; 0025; 0026, (2021/08/21)
The invention relates to the technical field of drug synthesis, and particularly discloses a preparation method of oseltamivir phosphate key intermediate hydrochloride, which comprises the following steps: reacting tert-butylamine with epoxide under the condition of taking anhydrous magnesium chloride as a catalyst to generate an intermediate product A; adding methanesulfonyl chloride and triethylamine to generate an intermediate product B; adding diallylamine and benzenesulfonic acid to generate an intermediate product C, and adding acetic anhydride and anhydrous sodium acetate to generate an intermediate product D; and preparing an intermediate product D ethanol solution, dropwise adding the intermediate product D ethanol solution into a saturated hydrogen chloride ethanol solution, conducting stirring, conducting standing, carrying out suction filtration, conducting washing, conducting pulping, carrying out suction filtration, and conducting drying. According to the preparation method disclosed by the invention, oseltamivir phosphate key intermediate hydrochloride is successfully separated and obtained, and the yield is relatively high.
Research and Development of a Second-Generation Process for Oseltamivir Phosphate, Prodrug for a Neuraminidase Inhibitor
Harrington, Peter J.,Brown, Jack D.,Foderaro, Tommaso,Hughes, Robert C.
, p. 86 - 91 (2013/09/04)
A second-generation manufacturing process from a shikimic acid-derived epoxide to oseltamivir phosphate features a magnesium chloride - amine complex-catalyzed ring opening of the epoxide by tert-butylamine, a selective O-sulfonylation of the resulting tert-butylamino alcohol, a surprisingly efficient cleavage of a tert-butyl group from an aliphatic tert-butylamide, and the isolation of oseltamivir phosphate from a palladium-catalyzed allyl transfer reaction mixture. The overall yield from the epoxide to oseltamivir phosphate has been increased from 27 to 29% or 35-38% for two previous processes, respectively, to 61%.
The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu): A challenge for synthesis & process research
Abrecht, Stefan,Harrington, Peter,Iding, Hans,Karpf, Martin,Trussardi, Rene,Wirz, Beat,Zutter, Ulrich
, p. 621 - 629 (2007/10/03)
The evolution of the synthesis of oseltamivir phosphate (Tamiflu), used for the oral treatment and prevention of influenza virus infections (viral flu) is described. Oseltamivir phosphate is the ethyl ester prodrug of the corresponding acid, a potent and selective inhibitor of influenza neuraminidase. The discovery chemistry route and scalable routes used for kilo laboratory production as well as the technical access to oseltamivir phosphate from (-)-shikimic acid proceeding via a synthetically well-developed epoxide building block followed by azide transformations are reviewed. Synthesis and process research investigations towards azide-free conversions of the key epoxide building block to oseltamivir phosphate are discussed. The search for new routes to oseltamivir phosphate independent of shikimic acid including Diels-Alder approaches and transformations of aromatic rings employing a desymmetrization concept are presented in view of large-scale production requirements.