The general procedure for the synthesis of 3-chloro-4-morpholino-1,2,5-thiadiazole from morpholine and 3,4-dichloro-1,2,5-thiadiazole was as follows: morpholine (6.75 g, 77.4 mmol) was added to a 100-mL three-necked flask assembled with a reflux condenser tube. The flask was heated to 110 °C and 3,4-dichloro-1,2,5-thiadiazole (3.0 g, 19.3 mmol) was slowly added dropwise over 20 min. After the dropwise addition was completed, the reaction temperature was kept at 110°C with stirring for 2 hours. After completion of the reaction, the reaction mixture was cooled to 0°C in an ice bath. Water (30 mL) was added and the mixture was acidified with concentrated hydrochloric acid. The mixture was stirred at 0 °C until a precipitate precipitated. The solid product was collected by filtration, washed with water and dried. The resulting orange solid was recrystallized by methanol and dried under high vacuum to give 3.5 g (87.9% yield) of 4-(4-chloro-1,2,5-thiadiazol-3-yl)morpholine. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 3.45-3.55 (m, 2H), 3.80-3.90 (m, 2H). Mass spectral analysis showed (M + H)+ = 206.1.
