Description
Boc-6-aminohexanoic acid is an alkane chain with terminal carboxlic acid and Boc-protected amino groups. The compound can be used as a PROTAC linker in the synthesis of PROTACs and other conjugation applications. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond. The Boc group can be deprotected under mild acidic conditions to form the free amine.
Synthesis
General procedure for the synthesis of tert-butoxycarbonyl 6-aminohexanoic acid from 6-aminohexanoic acid (20 g, 153 mmol) and di-tert-butyl dicarbonate (3.67 g, 16.8 mmol): 6-aminohexanoic acid was dissolved in dichloromethane (30 mL) followed by addition of di-tert-butyl dicarbonate. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the reaction mixture was filtered and the solvent was removed by distillation under reduced pressure. The crude product was dried under high vacuum to give 4.08 g (115% yield) of the target compound. The product was characterized by 400 MHz 1H NMR (DMSO-d6): δ 2.85 (q, J=13.2,6.8 Hz, 2H), 2.15 (t, J=1.2 Hz, 2H), 1.47-1.43 (m, 4H), 1.34 (s, 9H), 1.22-1.18 (m, 2H). the LCMS analysis showed m/z=232 [M +H]+.
References
[1] Organic and Biomolecular Chemistry, 2005, vol. 3, # 13, p. 2450 - 2457
[2] Patent: WO2009/26446, 2009, A2. Location in patent: Page/Page column 30
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 14, p. 4358 - 4369
[4] Chemical Communications, 2006, # 36, p. 3783 - 3785
[5] Synthesis, 1988, # 3, p. 259 - 261
