35459-13-3Relevant academic research and scientific papers
Efficient Synthesis of 2-Amino-1-Arylethanols Through a Lewis Base-Catalyzed SiCl4-Mediated Asymmetric Passerini-Type Reaction
Ayad, Tahar,Gernet, Aurélie,Pirat, Jean-Luc,Ratovelomanana-Vidal, Virginie,Virieux, David
supporting information, p. 6497 - 6500 (2020/10/30)
We herein report, a practical and efficient strategy for the synthesis of enantiomerically enriched 2-amino-1-arylethanols, a structural motif commonly encountered in the family of β-adrenergic blockers or agonists, through a Lewis base-catalyzed SiClsub
A Combined High-Throughput Screening and Reaction Profiling Approach toward Development of a Tandem Catalytic Hydrogenation for the Synthesis of Salbutamol
Leitch, David C.,Greene, Thomas F.,O'Keeffe, Roisin,Lovelace, Thomas C.,Powers, Jeremiah D.,Searle, Andrew D.
supporting information, p. 1806 - 1814 (2017/11/24)
A combined high-throughput screening and reaction profiling approach to the telescoping of two reductions in the synthesis of Salbutamol is described. Optimization studies revealed the beneficial effect of mildly acidic conditions, and the use of water as a cosolvent. Persistent formation of deoxygenated impurities using a Pd/C catalyst led to the initiation of reaction profiling studies, which revealed that the ketone intermediate formed after rapid debenzylation is the sole source of deoxygenated impurities, indicating that more rapid ketone hydrogenation should minimize this deoxygenation. A dual catalyst approach based on these insights has been developed, with both Pd/Pt and Ru/Pt catalyst systems as more selective than Pd-only systems. Based on reaction profiles that indicate the deoxygenation side reaction is first-order in the concentration of debenzylated ketone intermediate, Pt catalysts for rapid and selective ketone hydrogenation were paired with Pd and Ru catalysts known to perform selective debenzylation. Optimization of these dual catalyst processes led to conditions that were demonstrated on 20 g scale to prepare Salbutamol in 49% isolated yield after recrystallization.
One-pot synthesis of N-substituted β-amino alcohols from aldehydes and isocyanides
Cioc, R?zvan C.,Van Der Niet, Daan J. H.,Janssen, Elwin,Ruijter, Eelco,Orru, Romano V.A.
, p. 7808 - 7813 (2015/05/20)
A practical two-stage one-pot synthesis of N-substituted β-amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α-halo ketones, β-halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible.
Enantioselective synthesis of phenyl-ethanolamines through application of chiral sulfoxide
Sivakumar, Aathimanivelu V.,Lahoti, Anand M.,Bhat, Sujata V.
body text, p. 3338 - 3347 (2011/03/19)
Efficient enantioselective synthesis of (R)- and (S)-enantiomers of 2-(tert-butylamino)-1-(p-methoxyphenyl)-ethanol has been achieved in high enantiomeric excess by using asymmetric sulfoxide as a chiral auxiliary. The present synthetic approach was further extended to the asymmetric synthesis of (R)-salbutamol. Copyright Taylor & Francis Group, LLC.
Application of the chiral acyl anion equivalent, trans-1,3-dithiane 1,3-dioxide, to an asymmetric synthesis of (R)-salbutamol
Aggarwal, Varinder K.,Esquivel-Zamora, Blanca N.
, p. 8618 - 8621 (2007/10/03)
An enantioselective synthesis of (R)-salbutamol has been carried out using the chiral, C2 symmetric acyl anion equivalent, (1R,3R)-1,3-dithiane 1,3-dioxide, which undergoes addition to an aromatic aldehyde with very high stereocontrol at 0 °C. Pummerer reaction and work-up with lithium ethanethiolate generated the α-hydroxy thiolester in high yield and further transformations led to the target compound with high enantiomeric excess.
Resolution of albuterol acetonide
Caira, Mino R.,Hunter, Roger,Nassimbeni, Luigi R.,Stevens, Anne T.
, p. 2175 - 2189 (2007/10/03)
The (R)-enantiomer of albuterol has been isolated via resolution of albuterol acetonide with (2S,3S)-di-O-benzoyl- or (2S,3S)-di-O-toluoyltartaric acid. The absolute configuration of the resolved acetonide was assessed by 1H NMR analysis of its (R)-Mosher's ester, and confirmed by an X-ray crystal structure determination of the (R)-phenylethylurea derivative of the (S)-enantiomer.
