651324-07-1

Usage

Uses

Used in Pharmaceutical Synthesis:
Ethyl (3R,4R,5S)-4-N-acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate is used as a key intermediate in the production of Oseltamivir Phosphate (O701000), which is a prodrug for Oseltamivir (O701005). ethyl (3R,4R,5S)-4-N-acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate is essential for the synthesis of antiviral medications, particularly those targeting influenza viruses.
In the pharmaceutical industry, this intermediate is utilized for its ability to undergo specific chemical reactions that facilitate the formation of the desired active pharmaceutical ingredient (API). The synthesis process involves multiple steps, each carefully controlled to ensure the production of a high-quality, effective medication.
The role of ethyl (3R,4R,5S)-4-N-acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate in the synthesis of Oseltamivir Phosphate highlights its importance in the development of antiviral therapies. Its unique properties allow it to participate in reactions that lead to the formation of the final drug product, which can help in the treatment and prevention of influenza infections.
Given the growing need for effective antiviral medications, the use of ethyl (3R,4R,5S)-4-N-acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate as a synthetic intermediate is of significant importance. Its contribution to the development of Oseltamivir and related compounds underscores its value in the pharmaceutical sector and the broader field of medicinal chemistry.

Upstream product

• 651324-04-8 (3R,4S,5R)-[5-(tert-butylamino)-4-hydroxy-3-(pent-3-yloxy)]cyclohex-1-ene-1-carboxylic acid ethyl ester 
• 757965-01-8 (1S,5R,6R)-5-(1-ethyl-propoxy)-7-oxa-bicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester 
• 124-02-7 diallylamine 
• 108-24-7 acetic anhydride 
• 651324-06-0 ethyl (3R,4R,5S)-5-N,N-diallylamino-4-(1,1-dimethylethyl)amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate 
• 204254-96-6 (1S,5R,6S)-5-(pentan-3-yloxy)-7-oxabicyclo[4.1.0]hept-3-ene-3-carboxylic acid ethyl ester 

Downstream Products

• 196618-13-0 oseltamivir 
• 204255-11-8 oseltamivir phosphate 

Relevant academic research and scientific papers

The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu): A challenge for synthesis & process research

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.

Research and Development of a Second-Generation Process for Oseltamivir Phosphate, Prodrug for a Neuraminidase Inhibitor

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%.

Process for preparing 1,2-diamino compounds

The invention provides a multi-step process for preparing 1,2-diamino compounds of formula wherein R1, R1′, R2, R2′, R3 and R4 have the meaning given in the specification and pharmaceutically acceptable addition salts thereof, from 1,2-epoxides of formula wherein R1, R1′, R2 and R2′ have the meaning given in the specification.