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The racemic compound is reacted in a suitable solvent with 0.25\u2010mol equivalent of (<jats:italic>R<\/jats:italic>,<jats:italic>R<\/jats:italic>)\u2010tartaric acid. After the decomposition of the diastereomeric salt, the remaining racemic fraction is precipitated with half\u2010equivalent of fumaric acid, and the pure amlodipine enantiomer is obtained. A quarter equivalent of the same resolving agent, (<jats:italic>R<\/jats:italic>,<jats:italic>R<\/jats:italic>)\u2010tartaric acid has been also added to the mother liquor to obtain the other enantiomer. The advantage of this method is that both of the enantiomers of amlodipine could be obtained with high enantiomeric excess with the same resolving agent. The racemic excess can also be isolated and re\u2010resolved. Achiral reagents (urea and thiourea) have been added to the resolving agent. These neutral additives are incorporated as co\u2010crystals in the structure of the diastereomeric salts. The used solvate\u2010former solvents and achiral additives are structurally similar, and their presence can enable the fractional separation of the diastereomers. In addition, the racemate, the enantiomers, and some intermediate salts with high diastereomeric excess obtained in the resolution process of amlodipine have been also subjected to thermal (DSC, TG\/DTA\u2010EGA\u2010MS, and \u2010FTIR), analytical (FTIR spectroscopic), and structural (XRD) comparisons, which indicate that the key\u2010intermediate crystalline diastereomeric salts\u2014as solvates and co\u2010crystals\u2014inherit a kind of structural similarity from their related additives\u2014solvents (DMF, DMAA, and DMSO) or (thio)ureas, respectively.<\/jats:p>","DOI":"10.1002\/chir.23373","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T15:56:12Z","timestamp":1637250972000},"page":"374-395","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Enantiomeric separation of racemic amlodipine by sequential fractional crystallization through formation of diastereomeric salt solvates and co\u2010crystals of solvate\u2010like compounds with specific structure \u2014 A tandem resolution"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-8567","authenticated-orcid":false,"given":"Dorottya Fruzsina","family":"B\u00e1nhegyi","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry and Technology Budapest University of Technology and Economics  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f3ra","family":"Szolcs\u00e1nyi","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology Budapest University of Technology and Economics  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e1nos","family":"Madar\u00e1sz","sequence":"additional","affiliation":[{"name":"Department of Inorganic and Analytical Chemistry Budapest University of Technology and Economics  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emese","family":"P\u00e1lovics","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and Technology Budapest University of Technology and Economics  Budapest Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"535","article-title":"Memoires sur la relation qui peut exister entre la forme crystalline et al composition chimique, et sur la cause de la polarization rotatoire","volume":"26","author":"Pasteur L","year":"1848","journal-title":"Acad Sci"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja020454r"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cg100152c"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201402446"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/cg1015274"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22431"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/B917564D"},{"key":"e_1_2_11_9_1","first-page":"162","article-title":"Note de L. 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