2,4,6-Trichloropyrimidine (5) (3.158 g, 17.22 mmol) was mixed with acetone (60 mL) and the mixture was cooled to 0 °C. Morpholine (7) (1.05 equiv, 1.576 g, 18.09 mmol) was slowly added at 0 °C, followed by stirring of the reaction mixture at 0 °C for 15 min, then warmed up to room temperature and continued stirring for 15 min. The progress of the reaction was monitored by thin layer chromatography (TLC, the unfolding agent was a hexane solution of 20% ethyl acetate). After completion of the reaction, the reaction mixture was concentrated by rotary evaporator and further dried under high vacuum. The crude product was purified by silica gel column chromatography using hexane solution of 20% ethyl acetate as eluent to afford the major regional isomer 2-morpholino-4,6-dichloropyrimidine (10) (3.183 g, 13.6 mmol, 79% yield). Elemental analysis (C8H9N3OCl2) Calculated values: C, 41.05; H, 3.88; measured values: C, 42.27; H, 4.06. 1H-NMR (300 MHz, CDCl3) δ 6.40 (s, 1H), 3.82-3.70 (m, 4H), 3.65 (m, 4H). High Resolution Mass Spectrometry (HRMS) [M]+ Calculated value: C8H9N3OCl2, 234.0201; Measured value: 234.0196. secondary regioisomer 4-(2,6-dichloropyrimidin-4-yl)morpholine (11) (0.806 g, 3.444 mmol, 20% yield). 1H-NMR (300 MHz, CDCl3) δ 6.56 (s, 1H), 3.85-3.60 (m, 8H). 13C-NMR (101MHz, CDCl3) δ 161.75, 160.55, 108.31, 66.59, 44.39. HRMS [M]+ calculated value: C8H9N3OCl2, 234.0201; measured value: 234.0196.
