反应详情

温度

75 °C

Triethylorthoacetate (2.57 ml, 14 mmol) was added to a stirred, heated (75° C.) solution of methyl 3-amino-5-(trifluoromethyl)benzoate (the product of Description 1, step ii) (2.19 g, 10 mmol) in acetic acid (15 ml). The mixture was stirred at 75° C. for 45 minutes, then sodium azide (1.95 g, 30 mmol) was added in portions over 45 minutes. The mixture was stirred at 75° C. for 4 hours, cooled and poured into water (50 ml). The pH was adjusted to 7.0 with aqueous sodium hydroxide (4M) and the mixture was extracted with ethyl acetate (3×50 ml). The combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (2×50 ml) and brine (50 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate/hexane (30:70 increasing to 60:40) to give methyl 3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzoate as a yellow oil (1.62 g, 57%), 1H (CDCl3) δ 8.51 (1H, s), 8.36 (1H, s), 8.02 (1H, s), 4.03 (3H, s), and 2.71 (3H, s). m/z 287 (M+H+).

1. stirringThe mixture was stirred at 75° C. for 4 hours
2. temperaturecooled
3. extractionthe mixture was extracted with ethyl acetate (3×50 ml)
4. washThe combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (2×50 ml) and brine (50 ml)
5. dry with materialdried (MgSO4)
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel
8. washeluting with ethyl acetate/hexane (30:70 increasing to 60:40)