412006-68-9Relevant academic research and scientific papers
Optimization and scale-up of a suzuki#miyaura coupling reaction: Development of an efficient palladium removal technique
Bullock, Kae M.,Mitchell, Mark B.,Toczko, Jennifer F.
, p. 896 - 899 (2008)
A ligand - solvent - base screen was performed on a Suzuki-Miyaura coupling reaction, and the screening data, followed by a set of focused experiments, helped to optimize reaction conditions. Further work was carried out that centered on reducing the level of residual palladium in the isolated product. Treatment of the reaction mixture with toluene and 20% aqueous NaHSO3 at elevated temperature lowered the palladium content from ～8000 ppm to 100 ppm or less. The Suzuki - Miyaura coupling and palladium removal process were demonstrated on 20-L scale, are highly efficient and cost-effective, and require short cycle times.
General suzuki coupling of heteroaryl bromides by using tri-tert-butylphosphine as a supporting ligand
Zou, Yinjun,Yue, Guizhou,Xu, Jianwei,Zhou, Jianrong
supporting information, p. 5901 - 5905 (2015/03/30)
A general procedure for the fast Suzuki coupling of major families of heteroaryl bromides was realized by using Pd(OAc)2/PtBu3 as the catalyst. Many couplings were finished within minutes at room temperature in n-butanol. Different from previous studies, three typical heteroaryl bromides were systematically examined in couplings of various heteroaryl and aryl boronic acids. A fast, general coupling of heteroaryl bromides is realized by using a single palladium catalyst supported by tri-tert-butylphosphine.
Statistical DoE approach to the removal of palladium from active pharmaceutical ingredients (APIs) by functionalized silica adsorbents
Recho, Jan,Black, Richard J. G.,North, Christopher,Ward, James E.,Wilkes, Robin D.
supporting information, p. 626 - 635 (2014/06/09)
The influence of four parameters (temperature, scavenging time, amount of scavenger, and concentration of palladium in the solution) on the efficiency of Pd removal from a cross-coupling reaction, using a commercially available Pd scavenger, SPM32, was studied. The DoE-based method employed yielded more information than is readily attainable from standard adsorption isotherms and kinetics experiments. The optimal regime of scavenging was identified; intuitive and nonintuitive effects of temperature, scavenging time, and scavenger amounts were highlighted; and a mathematical model quantifying predicted Pd removal from the synthetic intermediate was built.
Palladium nanoparticles on graphite oxide: A recyclable catalyst for the synthesis of biaryl cores
Santra, Subhankar,Hota, Pradip Kumar,Bhattacharyya, Rangeet,Bera, Parthasarathi,Ghosh, Prasenjit,Mandal, Swadhin K.
, p. 2776 - 2789 (2014/01/06)
The synthesis of life saving drug molecules in a cost-effective and environmentally benign pathway is of paramount significance. We present an environment friendly protocol to prepare core moieties of top selling drug molecules such as boscalid and telmisartan using Suzuki-Miyaura coupling conditions. In contrast to the traditional synthesis of these pharmaceutically important molecules, we have accomplished a graphite oxide (GO) supported palladium nanoparticles (PdNPs) based catalyst which quantitatively produced these core biaryl moieties of top selling drug molecules in a recyclable way. The catalytic activity remained unchanged even after 16 successive catalytic cycles without incorporating any palladium metal impurity in the pharmaceutically significant organic products. A detailed study including IR spectroscopy, solid state NMR spectroscopy, X-ray photoelectron spectroscopy, and DFT calculation was employed to understand the role of solid support on the nondecaying recycling ability of the catalyst during the Suzuki-Miyaura coupling reaction. The study indicates a strong chemical interaction of the different functionalities present in the GO, with the palladium centers which is primarily responsible for such sustained catalytic activity during the consecutive Suzuki-Miyaura coupling cycles.
