Uses
4-Chloro-5-methoxypyrimidine is a heterocyclic compound that can be used as an intermediate in organic synthesis.
Synthesis
The general procedure for the synthesis of 4-chloro-5-methoxypyrimidine from 4-hydroxy-5-methoxypyrimidine was as follows: 5-methoxypyrimidin-4-ol (57 g, 0.452 mol) was suspended in phosphorous triclosan (540 mL) and heated to reflux for 6 hours. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent dichloromethane/methanol = 10:1), and after confirming the completion of the reaction, most of the phosphorous trichloride was evaporated under reduced pressure. The residue was slowly poured into ice water (2 L) and the pH was adjusted with potassium carbonate (250 g) to about 7. Subsequently, the mixture was extracted with ethyl acetate/tert-butyl methyl ether (3:1, 4 x 250 mL). The organic phases were combined, washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 4-chloro-5-methoxypyrimidine (3S g, 58% yield) as a yellow solid. Its 1H NMR (400 MHz, DMSO-d6) data were as follows: δ 8.63 (s, 1H), 8.32 (s, 1H), 4.02 (s, 3H).
References
[1] Journal of Organic Chemistry, 1997, vol. 62, # 26, p. 9192 - 9202
[2] Patent: WO2016/97918, 2016, A1. Location in patent: Page/Page column 80
[3] Organic Process Research and Development, 2015, vol. 19, # 6, p. 639 - 645
