4-(4-Aminophenyl)piperazine-1-carboxylic acid tert-butyl ester can be used as a standard or reference for the qualitative and quantitative analysis of impurities in the synthesis of related drugs, ensuring drug purity and quality control. For example, it can be used to detect process impurities in drugs containing the 4-(4-aminophenyl)piperazine structure, and assist in the development of drug quality standards.
The general procedure for the synthesis of tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate from tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate was as follows: first, tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate (8.2 g, 26.68 mmol) was dissolved in methanol (100 mL), followed by purging with nitrogen and depressurization. Next, 10% wet palladium carbon catalyst was added to the solution and the hydrogenation reaction was carried out under hydrogen pressure of 50 psi for 16 hours. Upon completion of the reaction, the mixture was filtered through diatomaceous earth to remove the catalyst, and the filtrate was subsequently concentrated under reduced pressure to afford tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate (7.4 g, 97% yield) as a dark blue oily product, which was used directly in subsequent reactions without further purification. The molecular formula of the product was C15H23N3O2, and the mass spectrometry analysis showed that the m/z was 277.9 (M + H).
[1] Patent: WO2006/38039, 2006, A1. Location in patent: Page/Page column 17; 30
[2] Patent: EP1215208, 2002, A2. Location in patent: Example C(101)
[3] Patent: WO2012/110773, 2012, A1. Location in patent: Page/Page column 52; 53
[4] Patent: WO2014/26242, 2014, A1. Location in patent: Page/Page column 77
[5] Patent: WO2014/27199, 2014, A1. Location in patent: Page/Page column 55
