332047-13-9Relevant academic research and scientific papers
A oseltamivir acetyl aziridine intermediate preparation method
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Paragraph 0033; 0034; 0035, (2018/09/21)
The invention discloses a oseltamivir (Oseltamivir) acetyl aziridine intermediate I (Figure 1) of the preparation method. In the method of the shikimic acid epoxy derivative II as raw materials, by the six chemical synthesis step (Figure 2) to make the oseltamivir acetyl aziridine intermediate I, yield is 44 - 61%. The invention comprises the following six chemical synthesis steps: (1) epoxy compound II of the 3 - position open-loop and through the one-pot three-step series formed by the reaction of 3, 4 - bit aziridine compound III; (2) 3 - pentanol selective attack 3 - bit open-loop to obtain compound IV; (3) 4 - bit removing allyl get compound V; (4) 4 - amino acetylation to obtain compound VI; (5) 5 - hydroxy methyl sulfonylation to obtain compound VII; (6) 4 - acetyl amino attack at the 5 - position of the ring to obtain the oseltamivir acetyl aziridine intermediate I.
New, azide-free transformation of epoxides into 1,2-diamino compounds: Synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu)
Karpf,Trussardi
, p. 2044 - 2051 (2007/10/03)
A new, azide-free transformation of the key precursor epoxide 6 to the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (1, Tamiflu) is described. This sequence represents a new and efficient transformation of an epoxide into a 1,2-diamino compound devoid of potentially toxic and hazardous azide reagents and intermediates and avoids reduction and hydrogenation conditions. Using catalytic MgBr2·OEt2 as a new, inexpensive Lewis acid, the introduction of the first amino function was accomplished by opening of the oxirane ring with allylamine followed by Pd/C-catalyzed deallylation to the amino alcohol 16. The introduction of the second amino group was then accomplished via an efficient reaction cascade involving a domino sequence preferably utilizing a transient imino protection. Selective acetylation of the resulting diamine 17 was achieved under acidic conditions providing the crystalline 4-acetamido-5-N-allylamino-derivative 18, which upon deallylation over Pd/C and phosphate salt formation afforded drug substance 1. The overall yield of this route from 6 of 35-38% exceeds the yield of the azide-based process (27-29%) and does not require any chromatographic purification.
