2-Chloro-1-methylpyridinium Iodide

Used Chemicals

• Boc-Pro-OH [B1188]
• H-Phe-OMe·HCl [P1278]
• 2-Chloro-1-methylpyridinium Iodide [C0903]
• Triethylamine [T0424]
• Dichloromethane

Procedure

Boc-Pro-OH (1.65 g, 7.65 mmol), 2-chloro-1-methylpyridinium iodide (1.95 g, 7.65 mmol) were added to solution of H-Phe-OMe･HCl (1.50 g，6.95 mmol) in dichloromethane (30 mL) at room temperature and triethylamine (3.40 mL, 24.3 mmol) was added dropwise in 3 min at 5 to 10 °C. After stirring for 3 h, solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed with 10% citric acid aq. (30 mL × 3), 5% sodium bicarbonate solution aq. (30 mL × 3) and brine (30 mL). The organic layer was dried over anhydrous sodium sulfate and filtered. After the removal of solvent under reduced pressure, the given crude was purified by column chromatography (hexane : EtOAc = 2 : 1) to give Boc-Pro-Phe-OMe (2.37 g，91%) as a slightly yellowish solid.

Experimenter's Comments

Consumption of stating material and formation of product was monitored by LCMS.

Analytical Data（Boc-Pro-Phe-OMe）

¹H NMR (400 MHz, DMSO-d6); δ 8.17–8.27 (m, 1H), 7.19–7.29 (m, 5H), 4.42–4.53 (m, 1H), 4.00–4.13 (m, 1H), 3.56–3.61 (m, 3H), 3.18–3.38 (m, 2H), 2.90–3.08 (m, 2H), 1.91–2.11 (m, 1H), 1.56–1.71 (m, 3H), 1.15-1.40 (m, 9H).

Lead Reference

• A facile synthesis of carboxamides by using 1-methyl-2-halopyridinium iodides as coupling reagents
  • E. Bald, K. Saigo, and T. Mukaiyama, Chem. Lett. 1975, 4, 1163.

References

• 1) A CONVENIENT METHOD FOR THE SYNTHESIS OF CARBOXYLIC ESTERS
  • T. Mukaiyama, M. Usui, E. Shimada, K. Saigo, Chem. Lett. 1975, 4, 1045.
• 2) A FACILE SYNTHESIS OF CARBOXAMIDES BY USING 1-METHYL-2-HALOPYRIDINIUM IODIDES AS COUPLING REAGENTS
  • E. Bald, K. Saigo, T. Mukaiyama, Chem. Lett. 1975, 4, 1163.
• 3) Asymmetric Decarboxylative Allylation of Oxindoles
  • V. Franckevičius, J. D. Cuthbertson, M. Pickworth, D. S. Pugh, R. J. K. Taylor, Org. Lett. 2011, 13, 4264.