Ruthenium-Catalyzed Ester Reductions Applied to Pharmaceutical Intermediates

Abstract

Ruthenium pincer complexes were synthesised and used for catalytic ester reductions under mild conditions (~ 5 bar of hydrogen). An experimental design approach was used to optimise the conditions for yield, purity and robustness. Evidence for the catalytically active ruthenium dihydride species is presented. Observed intermediates and side-products as well as time-course data were used to build mechanistic insight. The optimised procedure was further demonstrated through scaled-up reductions of two pharmaceutically relevant esters, both in batch and in continuous flow.

Batch and continuous flow asymmetric synthesis of anabolic-androgenic steroids via a single-cell biocatalytic Δ1-dehydrogenation and C17β-carbonyl reduction cascade

“…To address this issue, an Autichem flow reactor was examined, as this type of reactor was designed and demonstrated to be suitable for reaction systems containing slurry. 34 Unfortunately, using the Autichem flow reactor alone in the present study turned out to be not appropriate, since only unsatisfactory conversion was achieved after various attempts (data not shown), although clogging was indeed avoided.…”

Promising Catalytic Application by Pincer Metal Complexes: Recent Advances in Hydrogenation of Carbon‐Based Molecules

“…Furthermore, the Jamieson group disclosed the synthesized ruthenium pincer metal complexes and utilized them as catalysts for ester hydrogenation, and the resulting products are applicable in pharmaceuticals (Scheme 32). [155] The catalytic reaction was performed under mild reaction conditions, such as ∼5 bar of H 2 . The optimized conditions were applicable for the large‐scale reactions of pharmaceutically important esters that were reduced into alcohols and are presented in Table 33.…”

Fixed Bed Continuous Hydrogenations in Trickle Flow Mode: A Pharmaceutical Industry Perspective

“…The main benefit of Taylor–Couette reactors is good mixing (via axisymmetric toroidal vortices, also known as Taylor vortex flow, Taylor flow); when slurries are used in conjunction with a Taylor–Couette reactor, the mixing results in well dispersed suspensions of solids, allowing solids to be flowed. , GSK have used a Taylor–Couette reactor for a homogeneous hydrogenation that becomes heterogeneous during processing. However, in the GSK article the reactor is called a CSTR …”