反应详情

温度

110 °C

3-Chloro-N-hydroxy-4-isopropoxybenzimidamide (10 g, 43.7 mmol) was dissolved in DMF (219 ml) under nitrogen. The mixture was heated at about 110° C. for about 10 min. A solution of 4-cyanobenzoyl chloride (7.24 g, 43.7 mmol) dissolved in DMF (30 mL) was added dropwise over about 20 min and the reaction heated at about 110° C. for about 4 h. until LCMS shows reaction complete. The reaction was cooled in an ice bath and poured into rapidly stirred water (1000 mL). The resulting white precipitate was collected by vacuum filtration and washed with water. The precipitate was dissolved in methylene chloride and washed with 1 N HCl and then brine. The methylene chloride was dried over sodium sulfate, filtered, and evaporated. Heptane and DCM were added to the residue and the mixture heated until the DCM had boiled off after which the mixture was allowed to cool. Solids did not dissolve in hot heptane. The resulting solid was collected by vacuum filtration and washed with heptane to provide 4-(3-(3-chloro-4-isopropoxyphenyl)-1,2,4-oxadiazol-5-yl)benzonitrile (12.568 g, 37.0 mmol, 85% yield) as a tan solid: LCMS (Table 1, Method a) Rt=4.58 min.; MS m/z: 340.20 (M+H)+.

1. additionwas added dropwise over about 20 min
2. temperaturethe reaction heated at about 110° C. for about 4 h. until LCMS
3. customreaction complete
4. temperatureThe reaction was cooled in an ice bath
5. filtrationThe resulting white precipitate was collected by vacuum filtration
6. washwashed with water
7. dissolutionThe precipitate was dissolved in methylene chloride
8. washwashed with 1 N HCl
9. dry with materialThe methylene chloride was dried over sodium sulfate
10. filtrationfiltered
11. customevaporated
12. additionHeptane and DCM were added to the residue
13. temperaturethe mixture heated until the DCM
14. temperatureto cool
15. dissolutionSolids did not dissolve in hot heptane
16. filtrationThe resulting solid was collected by vacuum filtration
17. washwashed with heptane