Uses
N-tert-Butoxycarbonyl-3-bromopropylamine, is a versatile building block used in the synthesis of various pharmaceutical and biologically active compounds. It has been shown to be utilized in the synthesis of an active anti-HIV ethidium-arginine conjugate targeted against the viral TAR RNA sequence.
Synthesis
Benzyl N-(3-bromopropyl)carbamate synthesis: A solution of triphenylphosphine (9.4 g, 28.60 mmol) and carbon tetrabromide (7.5 g, 28.60 mmol) in dry THF was added dropwise (30 mL) to a solution of benzyl N-(3-hydroxypropyl)carbamate (3.0 g, 14.30 mmol) in the same solvent (30 mL). After 48 h of stirring at room temperature, the solution was filtrated to remove an insoluble solid. After evaporation of filtrate, the residue was dissolved in CH2Cl2 and the solution washed with H2O. The organic layer was dried over MgSO4. Removal of the solvent yielded an oily residue, which was purified by column chromatography (CH2Cl2 to MeOH). After evaporation of the solvents benzyl N-(3-bromopropyl)carbamate was obtained as an orange oil (3.2 g, 86.4 %).
Rf (silica-gel, CHCl3) = 0.5. 1H-NMR (300 MHz, CDCl3, ppm) δH 7.32 (5H, m, Cbz), 5.15 (1H, br s, CBzNH-), 5.06 (2H, s, Cbz), 3.39 (2H, t), 3.30 (2H, q), 2.06 – 1.96 (2H, m). 13C-NMR (75.5 MHz, CDCl3, ppm) δc 156.4, 136.3, 128.4, 128.0, 127.9, 66.6, 39.2, 32.3, 30.6.
References
[1] Patent: WO2012/95628, 2012, A1. Location in patent: Page/Page column 20
[2] Journal of Labelled Compounds and Radiopharmaceuticals, 1996, vol. 38, # 1, p. 31 - 40
[3] Journal of Organic Chemistry, 2000, vol. 65, # 26, p. 8979 - 8987
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 17, p. 5273 - 5281
[5] Journal of Medicinal Chemistry, 2001, vol. 44, # 19, p. 3175 - 3186
