(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium Hexafluorophosphate

Used Chemicals

• Boc-Pro-OH [B1188]
• H-Phe-OMe·HCl [P1278]
• (1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium Hexafluorophosphate [C2733]
• N,N-Diisopropylethylamine [D1599]
• Acetonitrile

Procedure

To a solution of H-Phe-OMe·HCl (0.98 g, 4.6 mmol) in acetonitrile (40 mL) N,N-diisopropylethylamine (1.2 g, 9.2 mmol), Boc-Pro-OH (0.99 g, 4.6 mmol) and (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (2.0 g, 4.6 mmol) were successively added at 5 °C then the mixture was stirred overnight at room temperature. The reaction solvent was removed under reduced pressure and the residue was dissolved to ethyl acetate. The organic layer was successively washed with 10% aqueous citric acid solution, 5% aqueous sodium bicarbonate solution and brine, dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by column chromatography (1:1 ethyl acetate / hexane on SiO₂), giving Boc-Pro-Phe-OMe as pale yellow solid (1.4 g, 80% yield).

Experimenter’s Comments

The reaction mixture was monitored by TLC (hexane / ethyl acetate = 1 : 1, Rf = 0.40).

Analytical Data（Boc-Pro-Phe-OMe）

¹H NMR (400 MHz, CDCl₃); δ 8.09–8.29 (m, 1H), 7.12–7.35 (m, 5H), 4.39–4.60 (m, 1H), 3.96–4.18 (m, 1H), 3.48–3.70 (m, 3H), 3.14–3.44 (m, 2H), 2.86–3.14 (m, 2H), 1.91–2.11 (m, 1H), 1.50–1.78 (m, 3H), 1.10-1.49 (m, 9H).

¹³C NMR (101 MHz, CDCl₃); δ 172.6, 172.2, 153.3, 137.3, 129.0 (2 C), 128.1 (2 C), 126.5, 78.3, 59.5, 53.4, 51.7, 46.4, 36.4, 30.7, 27.8 (3 C), 22.8.

Lead Reference

• Efficient α‐Helix Induction in a Linear Peptide Chain by N‐Capping with a Bridged‐tricyclic Diproline Analogue
  • V. Hack, C. Reuter, R. Opitz, P. Schmieder, M. Beyermann, J.-M. Neudörfl, R. Kühne, H.-G. Schmalz, Angew. Chem. Int. Ed. 2013, 52, 9539.

Other References

• COMU: A Safer and More Effective Replacement for Benzotriazole‐Based Uronium Coupling Reagents
  • A. El-Faham, R. S. Funosas, R. Prohens, F. Albericio, Chem. Eur. J. 2009, 15, 9404.

References

• COMU: A Safer and More Effective Replacement for Benzotriazole-Based Uronium Coupling Reagents
  • A. El-Faham, R. S. Funosas, R. Prohens, F. Albericio, Chem.Eur. J. 2009, 15, 9404.