Reaction Steps
2-(1-Chloro-ethyl)-5-(3-chloro-phenyl)-[1,3,4]oxadiazole (331 mg, 1.36 mmol) was mixed with dimethyl malonate (360 mg, 2/76 mmol) and DBU (207 mg, 1.36 mmol) in acetonitrile (3 ml) at 70° C. overnight. The reaction mixture was dilute with dichloromethane and washed with water. The organic layer was dried and concentrated. The residue was purified with 5˜20% ethyl acetate in hexanes to give 357 mg (74.3%) 2-{1-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-ethyl}-malonic acid dimethyl ester as white solid. 1H-NMR(CDCl3) d(ppm): 8.03 (s, 1H), 7.95 (d, 1H), 7.53 (d, 1H), 7.47 (t, 1H), 4.06 (d, 1H), 3.95 (m, 1H), 3.84 (s, 3H), 3.74 (s, 3H) and 1.51 (d, 3H). Step 2: 3-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid methyl ester: 2-{1-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-ethyl}-malonic acid dimethyl ester (352.8 mg, 1.0 mmol) was mixed with sodium chloride (76.3 mg, 1.3 mmol) and a drop of water in DMSO (1.5 ml) at 175° C. for an h. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was washed with water and concentrated. The residue was purified with column chromatography with 10˜20% ethyl acetate in hexanes to give 215 mg (76.8%)3-[5-(3-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid methyl ester as clear oil. 1H-NMR(CDCl3) d(ppm): 8.03 (s, 1H), 7.94 (d, 1H), 7.53 (d, 1H), 7.45 (t, 1H), 3.73 (s, 3H), 3.67 (m, 1H), 3.05 (dd, 1H), 2.73 (dd, 1H) and 1.50 (d, 3H). Step 3: 3-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid hydrazide: 3-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid hydrazide (146 mg, %) was obtained from 3-[5-(3-chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-butyric acid methyl ester (215 mg, 0.766 mmol) reacted with hydrazine hydrate (0.74 ml) in methanol (3 ml) at room temperature for 2.5 h. 1H-NMR(CDCl3) d(ppm): 8.03 (s, 1H), 7.94 (d, 1H), 7.53 (d, 1H), 7.46 (t, 1H), 7.23 (w, 1H), 3.93 (w, 2H), 3.71 (m, 1H), 2.90 (dd, 1H), 2.57 (dd, 1H) and 1.50 (d, 3H).
