Uses
4-Benzyloxycarbonylaminopiperidine is an intermediate in synthesizing 7-Ethyl-10-(4-amino-1-piperidino)carbonyloxycamptothecin (E899150), a major metabolite of Irinotecan.
Definition
ChEBI: Benzyl 4-piperidinylcarbamate is a member of piperidines.
Synthesis
The general procedure for the synthesis of 4-(N-benzyloxycarbonyl)-aminopiperidine from 1-Boc-4-(Cbz-amino)piperidine was as follows: tert-butyl 4-{[(benzyloxy)carbonyl]amino}piperidine-1-carboxylate (13.1 g, 39.2 mmol) obtained in Example 1a was mixed with a 5N aqueous hydrochloric acid (40 ml, 200 mmol) and a methanolic (40 ml) The mixture was stirred at room temperature for 23 hours. After completion of the reaction, 5N aqueous sodium hydroxide solution (40 ml) was slowly added to the reaction mixture under ice bath cooling conditions. Subsequently, water and solvent were removed from the reaction mixture by distillation while azeotropic distillation using ethanol was carried out to remove water completely. Ethanol was added to the distilled residue, filtered to remove insoluble matter, and the filtrate was concentrated to give the final 4-(N-benzyloxycarbonyl)-aminopiperidine (9.10 g, 99.1% yield). The product was characterized by 1H-NMR (400 MHz, CDCl3) with the following chemical shifts δppm: 1.31-1.42 (2H, m), 1.92-2.04 (2H, br), 2.70 (2H, d, J = 12Hz), 3.10 (2H, d, J = 12Hz), 3.56-3.68 (1H, br), 4.72- 4.81 (1H, br), 5.09 (2H, s), 7.26-7.40 (5H, m).
References
[1] Patent: US2013/65925, 2013, A1. Location in patent: Paragraph 0197; 0198
[2] Patent: EP2757103, 2014, A1. Location in patent: Paragraph 0149
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 3, p. 1021 - 1046
[4] Patent: WO2011/60321, 2011, A1. Location in patent: Page/Page column 115
[5] Patent: WO2006/99884, 2006, A1. Location in patent: Page/Page column 18
