Triethylamine → (R)-3-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid methyl ester

To a solution of (R)-2-methylsuccinic acid 4-methyl ester (2.2 g, 15 mmol) and triethylamine (4.54 g, 45 mmol) in THF (30 ml), isobutylchloroformate (2.16 g, 15.8 mmol) was added dropwise at 0° C. After being stirred for 30 min, the 3-chloro-N-hydroxy-benzamidine (2.56 g, 15 mmol) was added. The reaction mixture was stirred at room temperature for another 30 min and then heated to 135° C. with DMF for 45 min. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried and concentrated to give 4.0 g (95%) of (R)-3-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid methyl ester as pale-yellow oil. Step 2: (R)-3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid hydrazide: (R)-3-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid hydrazide (430 mg, 77%) was obtained from (R)-3-[3-(3-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-butyric acid methyl ester (461.4 mg, 2.0 mmol) reacted with hydrazine hydrate (2 mL) in methanol (2 mL) at 65° C. for 1 h. 1H-NMR(CDCl3) d (ppm): 8.07 (s, 1H), 7.96 (d, 1H), 7.46 (m, 2H), 6.98 (w, 1H), 3.93 (w, 2H), 3.78 (m, 1H), 2.86 (dd, 1H), 2.55 (dd, 1H) and 1.59 (d, 3H).

1. stirringThe reaction mixture was stirred at room temperature for another 30 min
2. washwashed with water and brine
3. customThe organic layer was dried
4. concentrationconcentrated

ORD record

ord-0619517595234c78b62e1921dfc3b21e

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456200B2