反应详情

To a stirred and ice-cooled solution of sodium methoxide (1.659 g, 30.7146 mmol) in methanol (50 ml), 4-methoxyphenylacetonitrile (3.728 g, 24.5717 mmol) and 1-azido-2-fluoro-4-trifluoromethyl-benzene (4.200 g, 20.4764 mmol) are added portion wise and the mixture is allowed attain room temperature spontaneously and refluxed overnight. The resulting reaction mixture is concentrated, added water, and extracted with chloroform (3×100 mL). The combined organic layers are dried over MgSO4, filtered and concentrated to afford a brownish gummy material (5.900 g, 82% mass balance). The crude residue is purified by column chromatography over silica gel (230-400 mesh), eluting with 15% ethylacetate in hexane, to obtain the title compound as a grey solid (0.120 g, 1.5% yield). A major impurity isolated and characterized is 5-(4-methoxy-phenyl)-3-(2-methoxy-4-trifluoromethyl-phenyl)-3H-[1,2,3]triazol-4-ylamine (2.400 g, ˜33% yield).

1. additionare added portion wise
2. customis allowed attain room temperature
3. temperaturerefluxed overnight
4. customThe resulting reaction mixture
5. concentrationis concentrated
6. additionadded water
7. extractionextracted with chloroform (3×100 mL)
8. dry with materialThe combined organic layers are dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a brownish gummy material (5.900 g, 82% mass balance)
12. customThe crude residue is purified by column chromatography over silica gel (230-400 mesh)
13. washeluting with 15% ethylacetate in hexane