{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:30:08Z","timestamp":1792553408817,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T00:00:00Z","timestamp":1449619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Advanced European Research Council Grant \u201cNovel Process Windows-Boosted Micro Process Technology\u201d","award":["267443"],"award-info":[{"award-number":["267443"]}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemSusChem"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cinnarizine, cyclizine, buclizine, and meclizine belong to a family of antihistamines that resemble each other in terms of a 1\u2010diphenylmethylpiperazine moiety. We present the development of a four\u2010step continuous process to generate the final antihistamines from bulk alcohols as the starting compounds. HCl is used to synthesize the intermediate chlorides in a short reaction time and excellent yields. This methodology offers an excellent way to synthesize intermediates to be used in drug synthesis. Inline separation allows the collection of pure products and their immediate consumption in the following steps. Overall isolated yields for cinnarizine, cyclizine, and a buclizine derivative are 82, 94, and 87\u2009%, respectively. The total residence time for the four steps is 90\u2005min with a productivity of 2\u2005mmol\u2009h\n                    <jats:sup>\u22121<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1002\/cssc.201501367","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T02:27:10Z","timestamp":1449714430000},"page":"67-74","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Continuous\u2010Flow Multistep Synthesis of Cinnarizine, Cyclizine, and a Buclizine Derivative from Bulk Alcohols"],"prefix":"10.1002","volume":"9","author":[{"given":"Svetlana","family":"Borukhova","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering and Chemistry Technische Universiteit Eindhoven  Den Dolech 2 5600 MB Eindhoven Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Chemistry Technische Universiteit Eindhoven  Den Dolech 2 5600 MB Eindhoven Netherlands"},{"name":"Department of Organic Chemistry Ghent University  Krijgslaan 281 (S4) 9000 Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Hessel","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Chemistry Technische Universiteit Eindhoven  Den Dolech 2 5600 MB Eindhoven Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,9]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1039\/9781849733076-00039"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/b602413k"},{"key":"e_1_2_6_3_1","first-page":"689","volume-title":"Comprehensive Organic Transformations, 2nd\u2005ed.","author":"Larock R. 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