Tamiflu is one of the most effective anti-influenza drugs, which is currently manufactured by Hoffmann-La Roche from shikimic acid. Owing to its importance, more than 60 synthetic routes have been developed to date, however most of the synthetic routes utilise the potentially hazardous azide chemistry making them not green, thus not amenable to easy scale up. Consequently, this study exclusively demonstrated safe and efficient handling of potentially explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous flow technology. The azide intermediates were safely synthesised in full conversions and >89 % isolated yields.
An efficient continuous flow process for the synthesis
of dolutegravir,
an active pharmaceutical ingredient (API) for HIV treatment, was investigated.
The synthetic procedure starts from a readily available benzyl-protected
pyran via six chemical transformations using continuous flow reactors.
The significant advantage of this flow process includes the reduction
of the overall reaction time from 34.5 h in batch to 14.5 min. The
overall yield of each reaction step improved dramatically upon flow
optimization. Another key feature of this synthesis is telescoping
multiple steps.
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