Synthesis of Vixotrigine, a Voltage- and Use-Dependent Sodium Channel Blocker. Part 2: Development of a Late-Stage Process was written by Chen, Robbie;Couming, Vincent;Guzowski, John Jr.;Irdam, Erwin;Kiesman, William F.;Kwok, Daw-Iong Albert;Liang, Wenli;Mack, Tamera;O’Brien, Erin M.;Opalka, Suzanne M.;Patience, Daniel;Sahli, Stefan;Walker, Donald G.;Osei-Yeboah, Frederick;Gu, Chaozhan;Zhang, Xin;Stockli, Markus;Stucki, Thiemo;Matzinger, Hanspeter;Kuhn, Roman;Thut, Michael;Grohmann, Markus;Haefner, Benjamin;Lotz, Joerg;Nonnenmacher, Michael;Cerea, Paolangelo. And the article was included in Organic Process Research & Development in 2020.Recommanded Product: 4-Benzyloxyphenol The following contents are mentioned in the article:
As vixotrigine (I·HCl) entered a later clin. phase for trigeminal neuralgia, the development of a sustainable late-stage process was required to meet the supply needs for formulation optimization, phase 3 clin. trials, and registration stability batches (this is the expected com. formulation). In this article, authors describe how the process was streamlined from the early supply route and a comprehensive control strategy was established. Process improvements included improving safety and scalability for a temperature-sensitive Grignard reaction, simplifying unit operations, removal of heterogenous conditions, and route redesign to afford a high yielding, one-pot sequential alkylation and amidation. Improvement in the salt formation step, combined with wet milling, resulted in improved particle properties with enhanced flow properties of the final active pharmaceutical ingredient. The process mass intensity was improved 65% while maintaining drug substance purity at more than 99.8%. This new process has been scaled up to generate metric ton quantities of drug substance. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Recommanded Product: 4-Benzyloxyphenol).
4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Recommanded Product: 4-Benzyloxyphenol
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem