2914-77-4Relevant articles and documents
Catalytic Intramolecular Coupling of Ketoalkenes by Allylic C(sp3)?H Bond Cleavage: Synthesis of Five- and Six-Membered Carbocyclic Compounds
Mita, Tsuyoshi,Sato, Yoshihiro,Uchiyama, Masashi
, (2020/02/05)
In the presence of a catalytic amount of cobalt(II) acetylacetonate/Xantphos in combination with trimethylaluminum, various ketoalkenes underwent an intramolecular cyclization reaction triggered by cleavage of the allylic C(sp3)?H bond, affording carbocyclic compounds with high regio- and diastereoselectivity. Mono-, bi-, and tricarbocyclic compounds were produced in good yields. One of the products thus obtained was derivatized into tramadol in four simple steps. Notably, these intramolecular cyclizations took place in the absence of a gem-disubstituent on the tethered carbon chain (without the Thorpe-Ingold effect). (Figure presented.).
Across-the-World Automated Optimization and Continuous-Flow Synthesis of Pharmaceutical Agents Operating Through a Cloud-Based Server
Fitzpatrick, Daniel E.,Maujean, Timothé,Evans, Amanda C.,Ley, Steven V.
supporting information, p. 15128 - 15132 (2018/10/31)
The power of the Cloud has been harnessed for pharmaceutical compound production with remote servers based in Tokyo, Japan being left to autonomously find optimal synthesis conditions for three active pharmaceutical ingredients (APIs) in laboratories in Cambridge, UK. A researcher located in Los Angeles, USA controlled the entire process via an internet connection. The constituent synthetic steps for Tramadol, Lidocaine, and Bupropion were thus optimized with minimal intervention from operators within hours, yielding conditions satisfying customizable evaluation functions for all examples.
Optimization of throughput in semipreparative chiral liquid chromatography using stacked injection
Taheri, Mohammadreza,Fotovati, Mohsen,Hosseini, Seyed-Kiumars,Ghassempour, Alireza
, p. 579 - 588 (2017/09/29)
An interesting mode of chromatography for preparation of pure enantiomers from pure samples is the method of stacked injection as a pseudocontinuous procedure. Maximum throughput and minimal production costs can be achieved by the use of total chiral column length in this mode of chromatography. To maximize sample loading, often touching bands of the two enantiomers is automatically achieved. Conventional equations show direct correlation between touching-band loadability and the selectivity factor of two enantiomers. The important question for one who wants to obtain the highest throughput is “How to optimize different factors including selectivity, resolution, run time, and loading of the sample in order to save time without missing the touching-band resolution?” To answer this question, tramadol and propranolol were separated on cellulose 3,5-dimethyl phenyl carbamate, as two pure racemic mixtures with low and high solubilities in mobile phase, respectively. The mobile phase composition consisted of n-hexane solvent with alcohol modifier and diethylamine as the additive. A response surface methodology based on central composite design was used to optimize separation factors against the main responses. According to the stacked injection properties, two processes were investigated for maximizing throughput: one with a poorly soluble and another with a highly soluble racemic mixture. For each case, different optimization possibilities were inspected. It was revealed that resolution is a crucial response for separations of this kind. Peak area and run time are two critical parameters in optimization of stacked injection for binary mixtures which have low solubility in the mobile phase.
