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TCI Practical Example: Condensation Using Di(N-succinimidyl) Carbonate

We are proud to present the condensation reaction of 3-(3,4-dimethoxyphenyl)propionic acid and 4-methylbenzylamine using di(N-succinimidyl) carbonate as a condensing agent.

Used Chemicals

• Di(N-succinimidyl) Carbonate [D1662]
• 3-(3,4-Dimethoxyphenyl)propionic Acid [D1953]
• 4-Methylbenzylamine [M0864]
• Triethylamine [T0424]
• Dichloromethane

Procedure

To a solution of compound 3-(3,4-dimethoxyphenyl)propionic acid (0.10 g, 0.48 mmol), di(N-succinimidyl) carbonate (0.19 g, 0.62 mmol) in dichloromethane (5.0 mL) was added triethylamine (0.086 mL, 0.62 mmol) at ambient temperature and stirred at same temperature for 30 minutes. The mixture was added 4-methylbenzylamine (0.078 mL, 0.62 mmol) and stirred at same temperature for 1 hour. After completion of the reaction, the solvent was removed under reduced pressure and the residue was purified by column chromatography (ethyl acetate:hexane = 3:7 - 1:1 on silica gel) to give 1 (0.13 g，87% yield) as a white solid.

Experimenter’s Comments

The reaction mixture was monitored by UPLC.

Analytical Data

compound 1

¹H NMR (400 MHz, CDCl₃); δ 7.10 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.78-6.70 (m, 3H), 5.58 (brs, 1H), 4.36 (d, J = 5.6 Hz, 2H), 3.85 (s, 3H), 3.83 (s, 3H), 2.94 (t, J = 7.6 Hz, 2H), 2.48 (t, J = 7.6 Hz, 2H), 2.32 (s, 3H).

Lead Reference

• A novel active ester synthesis reagent (N,N’-disuccinimidyl carbonate)
• • H. Ogura, T. Kobayashi, K. Shimizu, K. Kawabe, K. Takeda, Tetrahedron Lett. 1979, 49, 4745.

Other References

• Studies on Lactams IX. A Convenient Synthesis of Lactam Rings
• • H. Ogura K. Takeda, Heterocycles 1981, 15, 467.
• Synthesis and Reactivity Comparisons of 1-Methyl-3-Substituted Cyclopropene Mini-tags for Tetrazine Bioorthogonal Reactions
• • J. Yang, Y. Liang, J. Šečkutė, K. N. Houk, N. K. Devaraj, Chem. Eur. J. 2014, 20, 3365.