Synthesis
General procedure for the synthesis of 2,5-dimethyl-4,6-dichloropyrimidine from 6-hydroxy-2,5-dimethyl-4(1H)-pyrimidinone: 3.3 g (23.5 mmol) of 2,5-dimethyl-4,6-dihydroxypyrimidine was mixed with 15 ml of phosphorus trichloride and the reaction was carried out at reflux for 8 hours. After completion of the reaction, the reaction mixture was allowed to cool to room temperature and slowly poured into a mixture of ice and water. The aqueous phase was extracted with ethyl acetate and the organic phase was sequentially washed with saturated sodium bicarbonate solution and dried over magnesium sulfate. Subsequently, the solvent was evaporated to dryness under reduced pressure (2 kPa) to give 3.39 g of the target product (81% yield). Thin layer chromatography (TLC) analysis showed an Rf value of 0.9 (silica gel, eluent: 100% ethyl acetate).1H-NMR (CDCl3) data: δ 2.46 (s, 3H, Cl-CH=C-); 2.68 (s, 3H, N=C-CH3). Mass spectrometry (MS) analysis showed molecular ion peaks of 177/179 (MH+).
References
[1] Patent: US2006/52398, 2006, A1. Location in patent: Page/Page column 75
[2] Patent: WO2005/95357, 2005, A2. Location in patent: Page/Page column 173
[3] Patent: US4617393, 1986, A
[4] Patent: WO2011/150156, 2011, A2. Location in patent: Page/Page column 124
[5] Patent: US2008/58348, 2008, A1. Location in patent: Page/Page column 14
