Studies on the Continuous-Flow Synthesis of Nonpeptidal bis-Tetrahydrofuran Moiety of Darunavir

Abstract

The use of continuous-flow chemistry has shown to be an important tool in improving API manufacture. In the present paper, we report the use of continuous-flow reactors in the synthesis of the bicyclic side chain of antiretroviral Darunavir.

Understanding flow chemistry for the production of active pharmaceutical ingredients

“…Recent developments in API syntheses also include the flow synthesis of gefapixant citrate (MK-7264) ( Ren et al., 2020 ), ticagrelor ( Hugentobler et al., 2017 ), darunavir ( Leão et al., 2015 ), ciprofloxacin ( Armstrong et al., 2021 ), rufinamide ( Borukhova et al., 2016a ), among others.…”

Biocatalytic routes to anti-viral agents and their synthetic intermediates

“…[241][242][243] The mixture of 176 enantiomers could also be resolved through enzymatic acetylation. 241,244,245 BCL was additionally proven to be capable of resolving a diastereomeric mixture of 176. 246 Several multi-step, one-pot procedures that include lipase resolution have been published for the synthesis of 3-OH-bis-THF.…”

Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates

“…118 A three-step continuous flow process was developed by Miranda and co-workers for the asymmetric synthesis of its bicyclic sidechain (Scheme 20). 119 Alkene 45 was quantitatively converted into the corresponding ketone (46) by means of ozonolysis performed in a flow reactor equipped with an ozone generator. The ketone was next submitted to continuous flow reduction in an H-Cube Pro hydrogenation reactor using 5 wt% Ru/C as catalyst to obtain alcohol 47 in a quantitative yield.…”