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DOI: 10.1055/s-2005-923589
Mild and Efficient Synthesis of Fmoc-Protected Amino Azides from Fmoc-Protected Amino Alcohols
Publication History
Publication Date:
23 December 2005 (online)
Abstract
Fmoc-protected amino azides - key intermediates for monomers of oligomeric urea and guanidine - can be efficiently prepared from the corresponding amino alcohol through iodination followed by substitution with sodium azide. This synthetic route avoids the preparation, storage, and handling of the highly toxic azidic acid that is used in an alternative method.
Key words
amino azides - amino alcohols - iodine
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References and Notes
All compounds gave satisfactory analytical data. Described below are a representative procedure and spectral data for Fmoc-protected glutamate azide 2h. Fmoc-protected glutamate alcohol 1h (50 mg, 0.12 mmol) in dry CH2Cl2 was added to a pre-mixed (5 min) solution of PPh3 (94 mg, 0.36 mmol, 3 equiv), iodine (91 mg, 0.36 mmol, 3 equiv) and imidazole (41 mg, 0.6 mmol, 5 equiv) in 1.2 mL dry CH2Cl2. The reaction mixture was stirred at r.t. for 1.5 h. After completion of the reaction the solvent was evaporated at reduced pressure and the corresponding iodide was purified by silica gel column chromatography (10% EtOAc in hexane). The iodide was then dissolved in 0.5 mL DMF, mixed with NaN3 (39 mg, 0.6 mmol, 5 equiv with respect to alcohol 1h) and stirred at r.t. for 3.5 h. After solvent removal and silica gel column chromatography (10% EtOAc in hexane), azide 2h was obtained as a white solid in high yield. Yield 50 mg (94% overall from alcohol 1h); mp 65-66 °C. 1H NMR (CDCl3): δ = 1.47 (s, 9 H), 1.82-1.86 (m, 2 H), 2.29-2.36 (m, 2 H), 3.42-3.48 (m, 2 H), 3.75-3.87 (br m, 1 H), 4.23 (t, 1 H, J = 6.9 Hz), 4.38-4.50 (m, 2 H), 5.03 (d, 1 H, J = 7.7 Hz), 7.31-7.45 (m, 4 H), 7.61 (d, 2 H, J = 7.2 Hz), 7.79 (d, 2 H, J = 7.2 Hz). ESI-MS: m/z = 437.0 [M + H]+.
Additional list of 1H NMR of new compounds:
Compound 2g: 1H NMR (CDCl3): δ = 1.76-1.83 (m, 2 H), 2.29-2.31 (m, 2 H), 3.31-3.37 (m, 2 H), 3.72 (br m, 1 H), 4.20 (t, 1 H, J = 6.5 Hz), 4.37-4.50 (m, 2 H), 5.01 (d, 1 H, J = 7.9 Hz), 6.75 (s, 1 H), 7.18-7.29 (m, 17 H), 7.35-7.41 (m, 2 H), 7.57 (d, 2 H, J = 7.4 Hz), 7.74 (d, 2 H, J = 7.4 Hz).
Compound 2i: 1H NMR (CDCl3): δ = 1.42 (s, 6 H), 1.41-1.58 (m, 4 H), 2.06 (s, 3 H), 2.49 (s, 3 H), 2.56 (s, 3 H), 2.90 (s, 2 H), 3.16-3.31 (m, 4 H), 3.72 (br m, 1 H), 4.14 (t, 1 H, J = 6.5 Hz), 4.32-4.41 (m, 2 H), 5.30 (d, 1 H, J = 8.4 Hz), 6.34 (br s, 2 H), 7.24-7.27 (m, 2 H), 7.34-7.38 (m, 2 H), 7.54-7.55 (m, 2 H), 7.73 (d, 2 H, J = 7.4 Hz).
Compound 2j: 1H NMR (CDCl3): δ = 1.65 (s, 9 H), 2.93-2.99 (m, 2 H), 3.45-3.49 (m, 2 H), 4.17-4.22 (m, 2 H), 4.41-4.43 (m, 2 H) 4.98 (d, 1 H, J = 7.8 Hz), 7.27-7.41 (m, 6 H), 7.46-7.63 (m, 4 Hz), 7.76 (d, 2 H, J = 7.4 Hz), 8.14 (br s, 1 H).