Ethanol → 5-(Chloromethyl)-3-phenyl-1,2,4-oxadiazole

Temperature

80 °C

A mixture of benzonitrile (26.2 g), hydroxylamine hydrochloride (17.7 g), potassium carbonate (17.6 g) and 70% ethanol (250 ml) was stirred at 80° C. for 2 hours. The reaction mixture was cooled to room temperature, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolve in acetone (250 ml) and potassium carbonate (19.0 g) was added. This mixture was cooled to 0° C. and chloroacetyl chloride (21.9 ml) was added dropwise. After stirring for 1 hour, the reaction mixture was concentrated. Water was added to the residue, the residual crystals were filtered, washed with water and dissolved in ethyl acetate. This solution was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in xylene (250 ml), and refluxed with separating water. After 2 hours, the solution was concentrated and the remaining crystals were washed with hexane to obtain 5-(chloromethyl)-3-phenyl-1,2,4-oxadiazole (25.2 g, yield 51%) as pale-yellow crystals. m.p. 38-39° C.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with ethyl acetate
3. washThe ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride
4. dry with materialdried (MgSO4)
5. concentrationconcentrated
6. dissolutionThe residue was dissolve in acetone (250 ml)
7. additionpotassium carbonate (19.0 g) was added
8. temperatureThis mixture was cooled to 0° C.
9. additionchloroacetyl chloride (21.9 ml) was added dropwise
10. stirringAfter stirring for 1 hour
11. concentrationthe reaction mixture was concentrated
12. additionWater was added to the residue
13. filtrationthe residual crystals were filtered
14. washwashed with water
15. dissolutiondissolved in ethyl acetate
16. washThis solution was washed with an aqueous saturated solution of sodium chloride
17. dry with materialdried (MgSO4)
18. concentrationconcentrated
19. dissolutionThe residue was dissolved in xylene (250 ml)
20. temperaturerefluxed with separating water
21. waitAfter 2 hours
22. concentrationthe solution was concentrated
23. washthe remaining crystals were washed with hexane

ORD record

ord-fa249ad3dc9d425f8fbdc61c29ef8ea8

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06495581B1