78573-45-2Relevant articles and documents
Green method for catalyzing deprotection of tetrahydropyrane ether into hydroxyl compound
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Paragraph 0026-0028, (2022/03/17)
The invention provides a green method for catalyzing deprotection of tetrahydropyrane ether into hydroxyl compound, and belongs to the field of green organic chemistry. According to the method, under neutral, open and room-temperature conditions, acetonitrile is used as a reaction solvent, FeBr2 or FeBr3 is used as a catalyst, H2O2 is used as an oxidizing agent, and a tetrahydropyrane ether derivative is converted into a hydroxyl compound within a short time. According to the invention, the catalyst FeBr2 and FeBr3, the oxidizing agent H2O2 and the solvent acetonitrile used in the method are cheap and easy to obtain, the reaction time is short, the condition is mild, the method has wide functional group compatibility, post-treatment is simple, operation is easy, and the method is a current green, environment-friendly and safe method for deprotecting the tetrahydropyrane ether derivative into the hydroxyl compound and has wide application prospects.
Continuous-Flow Amide and Ester Reductions Using Neat Borane Dimethylsulfide Complex
?tv?s, Sándor B.,Kappe, C. Oliver
, p. 1800 - 1807 (2020/02/27)
Reductions of amides and esters are of critical importance in synthetic chemistry, and there are numerous protocols for executing these transformations employing traditional batch conditions. Notably, strategies based on flow chemistry, especially for amide reductions, are much less explored. Herein, a simple process was developed in which neat borane dimethylsulfide complex (BH3?DMS) was used to reduce various esters and amides under continuous-flow conditions. Taking advantage of the solvent-free nature of the commercially available borane reagent, high substrate concentrations were realized, allowing outstanding productivity and a significant reduction in E-factors. In addition, with carefully optimized short residence times, the corresponding alcohols and amines were obtained in high selectivity and high yields. The synthetic utility of the inexpensive and easily implemented flow protocol was further corroborated by multigram-scale syntheses of pharmaceutically relevant products. Owing to its beneficial features, including low solvent and reducing agent consumption, high selectivity, simplicity, and inherent scalability, the present process demonstrates fewer environmental concerns than most typical batch reductions using metal hydrides as reducing agents.
Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
Yamashita, Yasunobu,Tanaka, Ken-ichiro,Yamakawa,Asano,Kanda, Yuki,Takafuji,Kawahara, Masahiro,Takenaga, Mitsuko,Fukunishi, Yoshifumi,Mizushima
supporting information, p. 3339 - 3346 (2019/06/18)
The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM3R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.