2-Chloro-1,3-dimethylimidazolinium Hexafluorophosphate

• Boc-Pro-OH [B1188]
• H-Phe-OMe·HCl [P1278]
• CIP [C1651]
• HOAt
• N,N-Diisopropylethylamine [D1599]
• Acetonitrile

To a solution of H-Phe-OMe·HCl (0.99 g, 4.6 mmol) in acetonitrile (40 mL) N,N-diisopropylethylamine (1.8 g, 13.9 mmol), Boc-Pro-OH (0.99 g, 4.6 mmol), HOAt (0.63 g, 4.6 mmol) and CIP (1.3 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 in ethyl acetate. The organic layer was successively washed with 10% aqueous citric acid 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 (1.5 g, 87% yield).

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

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.

• Convergent Synthesis of (−)-Mirabazole C Using a Chloroimidazolidium Coupling Reagent, CIP
  • K. Akaji, N. Kuriyama, Y. Kiso, J. Org. Chem. 1996, 61, 3350.

• Efficient coupling of α,α-dimethyl amino acid using a new chloro imidazolidium reagent, CIP
  • K. Akaji, N. Kuriyama, Y. Kiso, Tetrahedron Lett. 1994, 35, 3315.