{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:14:43Z","timestamp":1788444883108,"version":"build-2803163510"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000185","name":"Defense Advanced Research Projects Agency","doi-asserted-by":"publisher","award":["Army W31P4Q-18-1-0001"],"award-info":[{"award-number":["Army W31P4Q-18-1-0001"]}],"id":[{"id":"10.13039\/100000185","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009238","name":"Virginia Commonwealth University","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100009238","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines emtricitabine and lamivudine. During batch scale-up to tens of grams, we found that the sequence featured a strong exotherm and evolution of hydrogen chloride and sulfur dioxide. Keeping gaseous byproducts in solution and controlling the temperature led to better outcomes. These reactions are ideal candidates for implementation in a continuous mesoscale system for the sake of superior control. In addition, we found that fast reagent additions at controlled temperatures decreased byproduct formation. Herein we discuss the flow implementation and the final reactor design that led to a system with a 141 g\/h throughput.<\/jats:p>","DOI":"10.1021\/acs.oprd.0c00146","type":"journal-article","created":{"date-parts":[[2020,5,13]],"date-time":"2020-05-13T18:03:56Z","timestamp":1589393036000},"page":"2271-2280","source":"Crossref","is-referenced-by-count":12,"title":["A Continuous Flow Sulfuryl Chloride-Based Reaction\u2500Synthesis\nof a Key Intermediate in a New Route toward Emtricitabine and Lamivudine"],"prefix":"10.1021","volume":"24","author":[{"given":"Juliana M.","family":"de Souza","sequence":"first","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23284-3068"]},{"name":"Universidade Federal de Sa\u0303o Carlos , , ,","place":["Sa\u0303o Carlos-SP, Brazil, 13565-905"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateo","family":"Berton","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23284-3068"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1239-533X","authenticated-orcid":true,"given":"David R.","family":"Snead","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University , , , ,","place":["Richmond, Virginia, United States, 23284-3068"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-8813","authenticated-orcid":true,"given":"D. 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