69038-73-9Relevant academic research and scientific papers
Total Synthesis of Entrectinib with Key Photo-Redox Mediated Cross-Coupling in Flow
Cordell, Morgan J.,Adams, Matt R.,Vincent-Rocan, Jean-Fran?ois,Riley, John G.
supporting information, (2021/12/30)
By using photo-redox catalysis in flow the newly marketed drug entrectinib (referred to by the brand name Rozlytrek) was synthesized in 6 linear steps from readily available building blocks under mild conditions. Evaluation of multiple intermediates for their use in the critical C?N amination step in flow led to the finding that more electron deficient aryl-halides achieve higher conversion to the desired product. Data supports that more electron rich aryl-halides undergo a significant amount of hydro-dehalogenation compared to the productive C?N bond formation. Through evaluating various entry points into the synthesis of entrectinib, shorter routes were identified albeit in low yields. The modularity of this route will allow chemists to rapidly synthesize a diverse library of compounds through this route. Via different synthetic intermediates, a scale-up route was discovered for the synthesis of entrectinib using photo-redox in flow in less steps than previously reported, highlighting the utility of flow chemistry in the pharmaceutical industry.
Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
Huy, Peter H.,Mbouhom, Christelle
, p. 7399 - 7406 (2019/08/20)
A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
The Conversion of tert-Butyl Esters to Acid Chlorides Using Thionyl Chloride
Greenberg, Jacob A.,Sammakia, Tarek
, p. 3245 - 3251 (2017/03/23)
The reaction of tert-butyl esters with SOCl2 at room temperature provides acid chlorides in unpurified yields of 89% or greater. Benzyl, methyl, ethyl, and isopropyl esters are essentially unreactive under these conditions, allowing for the selective conversion of tert-butyl esters to acid chlorides in the presence of other esters.
Intramolecular rearrangement of α-azidoperoxides: An efficient synthesis of tert-butyl esters
Pramanik, Suman,Reddy, Reddy Rajasekhar,Ghorai, Prasanta
, p. 1393 - 1396 (2015/03/30)
An unprecedented intramolecular rearrangement of α-azidoperoxides, promoted by simple organic base to provide tert-butyl esters, has been presented. Further, a one-pot methodology consisting of in situ generation of the α-azidoperoxides from corresponding aldehydes followed by base-promoted rearrangement to obtain the desired ester has also been executed. Relevant mechanistic studies, to provide the proof for intramolecular alkoxy transfer, are investigated.
A mesoporous organosilica grafted Pd catalyst (MOG-Pd) for efficient base free and phosphine free synthesis of tertiary butyl esters via tertiary-butoxycarbonylation of boronic acid derivatives without using carbon monoxide
Ghosh, Kajari,Molla, Rostam Ali,Iqubal, Md. Asif,Islam
, p. 3540 - 3551 (2015/06/25)
A mesoporous organosilica grafted palladium(ii) catalyst was synthesized and characterized using various spectroscopic techniques. Its catalytic activity was evaluated for the synthesis of tertiary butyl esters via tert-butoxycarbonylation of boronic acid
Preparation of tert-butyl esters via Pd-catalyzed tert-butoxycarbonylation of (hetero)aryl boronic acid derivatives
Wu, Yusheng,Li, Xinjian,Zou, Dapeng,Zhu, Helong,Wang, Yaping,Li, Jingya,Wu, Yangjie
supporting information, p. 1836 - 1839 (2014/05/06)
A novel protocol to synthesize tert-butyl esters from boronic acids or boronic acid pinacol esters and di-t-butyl dicarbonate has been successfully achieved. The cross-coupling reactions can produce up to 94% yields by using palladium acetate and triphenylphosphine as catalyst system, dioxane as a solvent. Moreover, a wide range of substrates including benzenes, pyridines, and quinolines boronic acids or boronic acid pinacol esters can fit with this system as well.
Synthesis of functionalized aryl fluorides using organolithium reagents in flow microreactors
Nagaki, Aiichiro,Uesugi, Yuki,Kim, Heejin,Yoshida, Jun-Ichi
supporting information, p. 705 - 708 (2013/05/08)
Flow on: Flow microreactors enable the generation of aryl lithium compounds and subsequent electrophilic fluorination with NFSI and N-fluorosultam. The reaction can be successfully accomplished to synthesize various aryl fluorides involving an electron-withdrawing, an electron-donating, and a sterically hindered functional group in good yields. Copyright
Domino catalysis in the direct conversion of carboxylic acids to esters
Held,Von Den Hoff,Stephenson,Zipse
supporting information; experimental part, p. 1891 - 1900 (2009/08/07)
The combined use of high concentration conditions, auxiliary bases, and new catalysts allows for the rapid synthesis of sterically hindered carboxylic acid esters at room temperature. Mechanistic analysis indicates the intermediate formation of acid anhydrides and subsequent rate-limiting transformation to the ester products.
Carboxylation and esterification of functionalized arylcopper reagents
Ebert, Greg W.,Juda, Wayne L.,Kosakowski, Robert H.,Ma, Bing,Dong, Liming,Cummings, Keith E.,Phelps, Mwita V. B.,Mostafa, Adel E.,Luo, Jianyuan
, p. 4314 - 4317 (2007/10/03)
Functionalized arylcopper reagents have been produced in good yields at 25 °C from activated copper and the corresponding functionalized aryl iodides without the need of traditional organolithium or Grignard precursors. These organocopper compounds will undergo carboxylation with CO2 to form the corresponding copper benzoates. In turn, these salts can be acidified to produce the functionalized aryl acids or treated with appropriate alkyl halides in the presence of a dipolar aprotic solvent to generate the corresponding aryl esters. This methodology permits the formation of functionalized organic acids and esters that could not be generated by the carboxylation of organomagnesium compounds.
