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Optimization of BR-8 synthesis

Łukasz S. Kaczmarek 1Andrzej Leś 1,2Łukasz Mucha 1Katarzyna Badowska-Rosłonek 1Justyna Kowalska 1Anna Rosa 1

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
2. University of Warsaw, Faculty of Chemistry, Żwirki i Wigury 101, Warszawa 02-089, Poland


The key step of the BR-8 API synthesis is the SN2 type reaction of BR-7, in witch the sulfonate group is substituted with ethylamine, to give an aminoderivative with inverse configuration:

The reaction was carried out at laboratory scale under various conditionsin order to achieve high yield and purity of the product. The reaction parameters were sampled into full 32 factorial experiment (type of the leaving substituent; the solvent used as a medium) and then following a series of four consecutive screenings of excess of amine and temperature of the reaction following one-dimensional search (keeping one variable constant and changing the other). Molar content of the crude reaction product was found with the use of the mass balance and the corresponding HPLC parameters. Based on the predicted molar content of reaction mixtures a series of reaction response surfaces was calculated. From analysis of original experimental data and the response surfaces it appears that there exists an optimal set of reaction parameters for BR-8 synthesis securing a high conversion ratio of about 80% yield and 97% purity of the crude product.


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Related papers

Presentation: Poster at VII Multidyscyplinarna Konferencja Nauki o Leku, by Łukasz S. Kaczmarek
See On-line Journal of VII Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2010-03-17 11:09
Revised:   2010-04-01 10:16