Uses
Methyl 6-bromohexanoate serves as an alkylating reagent that reacts with dimethyl iminodiacetate in dry acetonitrile under nitrogen to afford the IDA triester[6]. It also acts as an alkylating agent in the preparation of pyrimidine-based hydroxamic acids, where 2-(alkylthio)pyrimidin-4(3H)-ones are alkylated with the ester and the resulting esters are converted to hydroxamic acids by aminolysis with hydroxylamine[7].
Synthesis
1. Synthesis of methyl 6-bromohexanoate: Dissolve 5.01 g (25.7 mmol) of 6-bromohexanoic acid in 250 mL of methanol and introduce hydrogen chloride gas by vigorous bubbling for 2-3 minutes. The reaction mixture was stirred at 15-25°C for 3 hours. Upon completion of the reaction, the solvent was removed by concentration to give 4.84 g of yellow oily product in 90% yield. The product was characterized by 1H NMR (DMSO-d6): δ 3.58 (3H, s), 3.51 (2H, t), 2.29 (2H, t), 1.78 (2H, pentet), 1.62-1.27 ppm (4H, m).
References
[1] Patent: US2002/15705, 2002, A1
[2] Patent: US4436746, 1984, A
[3] Patent: US4539410, 1985, A
[4] Patent: EP2425861, 2012, A1
[5] Patent: US2012/65367, 2012, A1
[6]Kalita, B., & Nicholas, K. M. (2004). Synthesis of α-substituted iminodiacetate ligands: α-hexadienyl derivatives for the selection of lipoxygenase mimics. Tetrahedron, 60(47), 10771–10778.
https://doi.org/10.1016/j.tet.2004.08.029 [7]Jakubkiene, V., Valiulis, G. E., Schweipert, M., Zubriene, A., Matulis, D., Meyer-Almes, F.-J., & Tumkevicius, S. (2022). Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids. Beilstein Journal of Organic Chemistry, 18, 837–844.
https://doi.org/10.3762/bjoc.18.84
