3-Fluorobenzoic Acid → 3-(chloromethyl)-5-(3-fluorophenyl)-1,2,4-oxadiazole

Temperature

135 °C

DMF (10 ml) was added to a mixture of 3-fluorobenzoic acid (710 mg, 5.07 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI) (972 mg, 5.07 mmol), 1-hydroxybenzotriazole hydrate (HOBt) (685 mg, 5.07 mmol) and 2-chloro-N-hydroxy-acetamidine (500 mg, 4.61 mmol) at room temperature and then stirred overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. DMF (14 ml) was added to the residue and the resulting solution was heated at 135° C. for 3.5 h to effect cyclization to oxadiazole. After cooling the reaction mixture was washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. 3-Chloromethyl-5-(3-fluoro-phenyl)-[1,2,4]oxadiazole (383 mg, 35% yield over 2 steps, yellow oil) was obtained by flash chromatography on silica gel, using 5% ethyl acetate in hexane. 1H NMR (CDCl3), δ (ppm): 7.96 (d, 1H), 7.86 (m, 1H), 7.54 (m, 1H), 7.33 (m, 1H), 4.68 (s, 2H).

1. washwashed with water (3 times) and brine
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. additionDMF (14 ml) was added to the residue
6. temperatureAfter cooling the reaction mixture
7. washwas washed with water (3 times) and brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-cb10264e1beb42b283f6ff7711a4daa2

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07585881B2