Sodium Hydroxide → Methyl 3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)benzoate

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Reaction Conditions

Reaction Steps

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+).

Provenance & Evidence