3-Bromobenzonitrile → 3-(3-Bromophenyl)-5-methyl-1,2,4-oxadiazole

Potassium tert-butoxide (7.33 g, 65.4 mmol) was added over 5 minutes to ice chilled, stirred methanol under argon. After a further 5 min hydroxylamine hydrochloride (4.9 g, 70.43 mmol) was added in one portion and the resultant mixture stirred at room temperature for 1 h. A solution of 3-bromobenzonitrile (7.93 g, 43.6 mmol) in methanol (120 ml) was added in one portion and the mixture heated at reflux for 4 h, cooled filtered, and the filtrate evaporated in vacuo. The residue was refluxed in acetic anhydride (60 ml) for 3 h, cooled to room temperature and poured into ice-water (300 ml). The precipitate was filtered, washed with water, dried in vacuo and chromatographed on silica eluting with 0-10% ethyl, acetate-hexane gradient. Fractions containing desired product were pooled and evaporated in vacuo and the residue recrystallised from hexane to afford the title compound as colourless crystals (5.2 g, 50%).

1. temperaturechilled
2. temperaturethe mixture heated
3. temperatureat reflux for 4 h
4. temperaturecooled
5. filtrationfiltered
6. customthe filtrate evaporated in vacuo
7. temperatureThe residue was refluxed in acetic anhydride (60 ml) for 3 h
8. additionpoured into ice-water (300 ml)
9. filtrationThe precipitate was filtered
10. washwashed with water
11. customdried in vacuo
12. customchromatographed on silica eluting with 0-10% ethyl, acetate-hexane gradient
13. additionFractions containing desired product
14. customevaporated in vacuo
15. customthe residue recrystallised from hexane

ORD record

ord-92889747bee847ea9ca3a01fcc1ce806

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06605607B1