General procedure for the synthesis of 2-(chloromethyl)pyrimidine from 2-pyrimidine methanol: To a stirred solution of pyrimidin-2-ylmethanol (4.5 g, 40.90 mmol) in dichloromethane (DCM, 50 mL) was slowly added thionyl chloride (SOCl2, 10 mL) at 0 °C and protected by an inert atmosphere. The reaction mixture was gradually warmed to 50 °C and stirred continuously for 2 hours. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the complete conversion of the feedstock, the volatiles were removed by distillation under reduced pressure. The residue was quenched with ice-cold water and subsequently neutralized with saturated sodium bicarbonate (NaHCO3) solution and extracted with ethyl acetate (EtOAc). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography to afford 2-(chloromethyl)pyrimidine in brown liquid form (960 mg, 18% yield). The product was characterized as follows: 1H-NMR (DMSO-d6, 400 MHz): δ8.84 (d, 2H), 7.52 (t, 1H), 4.82 (s, 2H); Mass spectrometry (ESI): m/z 128.5 [M + 1]+; Liquid Chromatography-Mass Spectrometry (LC-MS) purity: 95.09% (column: Chromolith RP-18, 100×4.6 mm; retention time: 3.86 min; mobile phase: 5 mM NH4OAc/acetonitrile (ACN); flow rate: 0.8 mL/min); thin-layer chromatography (TLC) conditions: 70% ethyl acetate/hexane (Rf value: 0.6).
