Arvind Girkar, Dujon Noronha, Prashant B. Patil, Mustapha Mandewale, Sudhir Sawant, Mohan Anand Chandavarkar and Kishor More*,
{"title":"An Improved Commercial Process for the Preparation of Lifitegrast","authors":"Arvind Girkar, Dujon Noronha, Prashant B. Patil, Mustapha Mandewale, Sudhir Sawant, Mohan Anand Chandavarkar and Kishor More*, ","doi":"10.1021/acs.oprd.4c0035610.1021/acs.oprd.4c00356","DOIUrl":null,"url":null,"abstract":"<p >A straightforward, efficient, and scalable commercial manufacturing process was developed for the ophthalmic anti-inflammatory drug lifitegrast via a novel ester intermediate from commercially available starting materials. Lifitegrast (Xiidra) was approved by the FDA on July 11, 2016, for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. The breakthrough step of this new process is the discovery of an <i>N</i>-Boc deprotection reaction that simultaneously transesterifies an intermediate to a new ester by using oxalyl chloride, which has favorable isolation properties. As a result of transesterification, the hydrolysis of the new ester intermediate occurs under milder conditions, which improves the quality of the product by reducing racemization. Lifitegrast prepared from this new process complied with the quality guidelines, as per the International Council for Harmonization (ICH). By using this new process, lifitegrast was produced on a 2 kg scale with an overall yield of 66%.</p>","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"28 12","pages":"4374–4379 4374–4379"},"PeriodicalIF":3.1000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Process Research & Development","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.oprd.4c00356","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
引用次数: 0
Abstract
A straightforward, efficient, and scalable commercial manufacturing process was developed for the ophthalmic anti-inflammatory drug lifitegrast via a novel ester intermediate from commercially available starting materials. Lifitegrast (Xiidra) was approved by the FDA on July 11, 2016, for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. The breakthrough step of this new process is the discovery of an N-Boc deprotection reaction that simultaneously transesterifies an intermediate to a new ester by using oxalyl chloride, which has favorable isolation properties. As a result of transesterification, the hydrolysis of the new ester intermediate occurs under milder conditions, which improves the quality of the product by reducing racemization. Lifitegrast prepared from this new process complied with the quality guidelines, as per the International Council for Harmonization (ICH). By using this new process, lifitegrast was produced on a 2 kg scale with an overall yield of 66%.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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