Ethanol → HCID 178472141, compound

Temperature

50 °C

To a ethanol solution (40 ml) of cyano-acetic acid ethyl ester (9.9 g, 0.1 mol), the mixture solution of sodium hydroxide (4 g, 0.1 mol) in water (40 ml) and 5 M hydroxylamine hydrochloride (20 ml) was added and the reaction mixture was stirred at 50° C. overnight. After being concentrated, the reaction mixture was diluted with water and extrated with ethyl acetate. The organic layer was dried, concentrated again. The residue was purified by column chromatography with 30˜70% ethyl acetate in hexanes to give 3.32 g (22.7%) of (N-Hydroxycarbamimidoyl)-acetic acid ethyl ester as white solid. 1H-NMR(CDCl3) d(ppm): 5.04 (ws, 2H), 4.20 (q, 2H), 3.19 (s, 2H) and 1.30 (t, 3H). Step 2: [5-(3-Chloro-phenyl)-[1,2,4]oxadiazol-3-yl]-acetic acid ethyl ester: To a dichloromethane solution (10 ml) of (N-hydroxycarbamimidoyl)-acetic acid ethyl ester (1.46 g, 10 mmol) and triethylamine, 3-chlorobenzoyl chloride (1.75 g, 10 mmol) was added slowly at 5° C. and the reaction mixture was stirred for 10 min. DMF (8 ml) was added to the reaction mixture was heated to 135° C. for 2 h. Standard work-up, the product was passed column with dichloromethane to give 1.2 g (45%) of [5-(3-chloro-phenyl)-[1,2,4]oxadiazol-3-yl]-acetic acid ethyl ester as pale-yellow oil. 1H-NMR(CDCl3) d(ppm): 8.168 (s, 1H), 8.04 (d, 1H), 7.59 (d, 1H), 7.49 (t, 1H), 4.26 (q, 2H), 3.91 (s, 2H) and 1.31 (t, 3H). Step 3: [5-(3-Chloro-phenyl)-[1,2,4]oxadiazol-3-yl]-acetic acid hydrazide: 5-(3-Chloro-phenyl)-[1,2,4]oxadiazol-3-yl]-acetic acid ethyl ester (0.64 g, 2.4 mmol) was mixed with 37% hydrazine (1.6 ml) in ethabol (10 ml) at 80° C. for 4 h. The reaction mixture was concentrated and diluted with water. The precipitate was filtered, washed with water to give 0.51 g (83.3%) of [5-(3-chloro-phenyl)-[1,2,4]oxadiazol-3-yl]-acetic acid hydrazide.

1. concentrationAfter being concentrated
2. additionthe reaction mixture was diluted with water
3. customThe organic layer was dried
4. concentrationconcentrated again
5. customThe residue was purified by column chromatography with 30˜70% ethyl acetate in hexanes

ORD record

ord-9c4dd529d33b4543a2db76cf4c924a1b

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456200B2