Babu K.C.,Inogent Laboratories |
Babu K.C.,Jawaharlal Nehru Technological University |
Reddy R.N.,Inogent Laboratories |
Rao S.Y.,Inogent Laboratories |
And 2 more authors.
(Chemical Equation Presented) A new approach for the asymmetric synthesis of (4S,5S)-cytoxazone 1 in five steps and in 48% overall yield starting from commercially available (R)-epichlorohydrin has been described. The key step include stereoselective 1,2-addition of p-methoxyphenyl magnesium bromide (p-OMePhMgBr) to chiral N-sulfinimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA, which gave corresponding sulfinamide 2 with high diastereoselectivity. Deprotection of the t-butylsulfonyl group and 1,3-dimethyl acetal in a single step followed by N-Boc protection and subsequent carbonylation yields the targeted (4S,5S)-cytoxazone 1. Copyright © Taylor & Francis Group, LLC. Source
Ripin D.H.B.,Clinton Health Access Initiative |
Teager D.S.,Clinton Health Access Initiative |
Fortunak J.,Howard University |
Basha S.M.,Aptuit Laurus Private Ltd |
And 21 more authors.
Organic Process Research and Development
The three-step manufacturing process used in the synthesis of tenofovir disoproxil fumarate (1) was studied and optimized, leading to a more productive and robust process. The yield was improved from about 13% overall to 24%. Key process improvements identified included implementation of a telescoped process for the second stage that obviated the need for an extraction and solvent exchange, and significant optimization of the final reaction, including the beneficial effect of adding a quaternary ammonium salt to the alkylation reaction and development of a nonaqueous process for removal of NMP and triethylamine from the product mixture to decrease the level of decomposition of product during the isolation. © 2010 American Chemical Society. Source