Description
Boc-5-aminopentanoic acid can be used as a PROTAC linker in the synthesis of PROTACs. Boc-5-aminopentanoic acid is an alkane chain with terminal carboxlic acid and Boc-protected amino groups. 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
Example 4: To a mixed solution of 100 mL of 2% aqueous sodium hydroxide and 100 mL of dioxane containing 5-aminopentanoic acid (5.85 g, 0.05 mol), a solution of dioxane containing di-tert-butyl dicarbonate (10.9 g, 0.05 mol) was slowly added dropwise. The reaction mixture was stirred at room temperature for 18 h and then acidified with 1 N hydrochloric acid to pH 3. The acidified reaction mixture was extracted three times with dichloromethane. The organic layers were combined, washed sequentially with water and dried over sodium sulfate, and concentrated under reduced pressure to give 10.1 g (93.5% yield) of 5-(tert-butoxycarbonylamino)pentanoic acid as a white crystalline solid.
References
[1] Journal of the American Chemical Society, 2018, vol. 140, # 44, p. 14599 - 14603
[2] ChemMedChem, 2016, p. 1172 - 1187
[3] ChemMedChem, 2016, vol. 11, # 11, p. 1172 - 1187
[4] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 4, p. 402 - 407
[5] Patent: US4476228, 1984, A
