{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T23:33:50Z","timestamp":1777419230989,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MIUR","award":["P1-0230"],"award-info":[{"award-number":["P1-0230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cinacalcet (I), sold as hydrochloride salt, is a calcimimetic drug which has been approved for the treatment of secondary hyperparathyroidism in patients with chronic renal disease and for the treatment of hypercalcemia in patients with parathyroid carcinoma. Here, an improved method for the synthesis of 3-(3-trifluoromethylphenyl)propanal (II), a key intermediate for the preparation of I, is described. The protocol required a Mizoroki\u2013Heck cross-coupling reaction between 1-bromo-3-(trifluoromethyl)benzene and acroleine diethyl acetal, catalyzed by Pd(OAc)2 in the presence of nBu4NOAc (tetrabutylammonium acetate), followed by the hydrogenation reaction of the crude mixture of products in a cascade process. Palladium species, at the end of the reaction, were efficiently recovered as Pd\/Al2O3. The procedure was developed under conventional heating conditions as well as under microwave-assisted conditions. The obtained mixture of 1-(3,3-diethoxypropyl)-3-(trifluoromethyl)benzene (III), impure for ethyl 3-(3-trifluoromethylphenyl) propanoate (IV), was finally treated, under mild conditions, with potassium diisobutyl-tert-butoxyaluminum hydride (PDBBA) to obtain after hydrolysis 3-(3-trifluoromethylphenyl)propanal (II), in an excellent overall yield and very high purity. Microwave conditions permitted a reduction in reaction times without affecting selectivity and yield. The final API was obtained through reductive amination of (II) with (R)-(+)-1-(1-naphthyl)ethylamine (V) using a catalyst prepared by us with a very low content of precious metal.<\/jats:p>","DOI":"10.3390\/molecules28166042","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T11:07:10Z","timestamp":1692011230000},"page":"6042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improved Process for the Synthesis of 3-(3-Trifluoromethylphenyl)propanal for More Sustainable Production of Cinacalcet HCl"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6208-9879","authenticated-orcid":false,"given":"Vikas Damu","family":"Rathod","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Molecolari e Nanosistemi, Universit\u00e0 Ca\u2019 Foscari Venezia, Via Torino 155, 30170 Venezia Mestre, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2116-3389","authenticated-orcid":false,"given":"Stefano","family":"Paganelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Molecolari e Nanosistemi, Universit\u00e0 Ca\u2019 Foscari Venezia, Via Torino 155, 30170 Venezia Mestre, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marijan","family":"Ko\u010devar","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ve\u010dna pot 113, SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marko","family":"Krivec","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ve\u010dna pot 113, SI-1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8948-2218","authenticated-orcid":false,"given":"Oreste","family":"Piccolo","sequence":"additional","affiliation":[{"name":"SCSOP, Via Born\u00f2 5, 23896 Sirtori, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,13]]},"reference":[{"key":"ref_1","unstructured":"(2023, August 08). 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