Methyl 6-(hydroxymethyl)nicotinate

Uses

Methyl 6-(hydroxymethyl)nicotinate serves as a precursor for synthesizing methyl 6-(azidomethyl)nicotinate and methyl 6-formylpyridine-3-carboxylate, the latter obtained via oxidation with DMP[1][2].

Synthesis

Step 1. Synthesis of methyl 6-(hydroxymethyl)nicotinate (55): a mixture of methyl 2,5-pyridinedicarboxylate (54; 100.0 g, 0.51 mol), CaCl2 (227.4 g, 2.05 mol), and THF (1100 mL) was mixed with EtOH (1200 mL), and stirred for 30 min. NaBH4 (48.6 g, 1.28 mol) was added in batches at 0 °C. The reaction mixture was stirred at room temperature for 18 hours. Subsequently, saturated NH4Cl solution (1.5 L) and water (2.0 L) were added slowly and extracted with dichloromethane (3 x 3.0 L). The organic phases were combined, dried with MgSO4 and concentrated under reduced pressure to give methyl 6-(hydroxymethyl)nicotinate 55 (82.0 g, 96% yield).

References

[1] Uttamapinant, C., Sanchez, M. I., Liu, D. S., Yao, J. Z., White, K. A., Grecian, S., Clark, S., Gee, K. R., & Ting, A. Y. (2013). Site-specific protein labeling using PRIME and chelation-assisted click chemistry. Nature Protocols, 8(8), 1620–1634. https://doi.org/10.1038/nprot.2013.096
[2] Smirnov, D. E., & Bezzubov, S. I. (2025). Synthesis, Structure, and Optical and Electrochemical Properties of a Chromophoric Cyclometalated Iridium(III) Complex. Russian Journal of Coordination Chemistry, 51(6), 514–521. https://doi.org/10.1134/s1070328425600561