3-Fluoro-4-methylpyridine

3-Fluoro-4-methylpyridine is used as an optimal cosubstrate to form amino acid catalyst complexes spontaneously at room temperature under basic conditions[6]. 3-Fluoro-4-methylpyridine serves as an efficient directing group in metathesis reactions[7].

3-Fluoro-4-methylpyridine To a cooled (-78℃) solution of N, N-diisopropylamine (15.92mL, 113.4mmol) in THF (14OmL) a solution of BuLi 2.5M in hexane (45.4ml, 113.4 mmol) was added dropwise over 30 minutes under an atmosphere of Argon. The mixture was stirred for 30 min. at - 78℃ and a solution of 3-fluoropyridine (10g, 103.1 mmol) in THF (5ml) was added. After 1h at -780C, the mixture was treated with MeI (7 ml, 113.4mmol) and then was allowed to reach 250C. A solution of NaHCO3 saturated (30ml) was added and the aqueous phase was extracted with diethyl ether. The organic layer was dried (MgSO4) and upon distillation the product was collected as a colourless liquid 3-Fluoro-4-methylpyridine, bp 1300C, yield 5.3 g (47percent).

[1] Patent: WO2007/17096,  2007,  A1. Location in patent: Page/Page column 70-71
[2] Journal of Medicinal Chemistry,  2003,  vol. 46,  # 4,  p. 461 - 473
[3] Patent: US6455532,  2002,  B1
[4] Patent: US6350745,  2002,  B1. Location in patent: Page column 15;16
[5] Patent: WO2006/35967,  2006,  A1. Location in patent: Page/Page column 98-99
[6]Reimets, N., Ausmees, K., Vija, S., Trummal, A., Uudsemaa, M., & Reile, I. (2023). Parahydrogen hyperpolarized NMR detection of underivatized short oligopeptides. The Analyst, 148(21), 5407–5415. https://doi.org/10.1039/d3an01345f
[7]Zhu, J., Zhang, R., & Dong, G. (2021). Orthogonal cross-coupling through intermolecular metathesis of unstrained C(aryl)–C(aryl) single bonds. Nature Chemistry, 13(9), 836–842. https://doi.org/10.1038/s41557-021-00757-4