反应详情

To a solution of 3,3-dimethyl-5-[1,2,4-triazol-1-ylmethyl]-3H-isobenzofuran-1-one (4.47 g Intermediate 1) in N,N-dimethylformamide (250 ml) at 0° under nitrogen was added potassium tert-butoxide (4.53 g). After one hour 3,5-difluoronitrobenzene (3.22 g) was added and stirring continued for five hours. The reaction mixture was partitioned between water and ethyl acetate and the phases separated. The aqueous phase was extracted with ethyl acetate and the combined organic extracts were washed with water and brine, dried and then evaporated to yield a brown oil. This was purified by column chromatography on Merck 9385 silica eluting initially with dichloromethane through to a 50:1 mixture of dichloromethane:methanol to yield a brown foam. The brown foam was further purified by gradient elution HPLC (water-acetonitrile-trifluoroacetic acid) to give 5-[(2,6-difluoro-4-nitrophenyl)-1,2,4-triazol-1-ylmethyl]-3,3-dimethyl-3H-isobenzofuran-1-one as a yellow foam.

1. customThe reaction mixture was partitioned between water and ethyl acetate
2. customthe phases separated
3. extractionThe aqueous phase was extracted with ethyl acetate
4. washthe combined organic extracts were washed with water and brine
5. customdried
6. customevaporated
7. customto yield a brown oil
8. customThis was purified by column chromatography on Merck 9385 silica eluting initially with dichloromethane through to a 50:1 mixture of dichloromethane
9. custommethanol to yield a brown foam
10. customThe brown foam was further purified by gradient elution HPLC (water-acetonitrile-trifluoroacetic acid)