Acetic Anhydride → 2-Methyl-6-(1H-1,2,4-triazol-1-yl)pyridin-3-yl acetate

Participants

Reaction Conditions

Reaction Steps

A solution of boron trifluoride etherate (217 μL, 1.7 mmol) in dimethylformamide (1 mL) was cooled to −15° C. using an ice-acetonitrile bath, and then stirred for 15 min at this temperature. A solution of 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamine (from Step 2; 200 mg, 1.14 mmol) in 1,2-dimethoxyethane (7 mL) was added dropwise to the solution at −15° C. and the stirring was continued for a further 15 min. tert-Butyl nitrite (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 90%; 157 mg, 1.4 mmol) was added dropwise, and the reaction mixture was stirred at −15° C. for 15 min and then at 0° C. for 1 h. Hexane (10 mL) was added and the solid was filtered off, washed with hexane, and air-dried. The solid was added to acetic anhydride (5 g, 49 mmol) and the mixture was heated at 100° C. for 1.5 h. The acetic anhydride was evaporated under high vacuum and then 1 M aqueous sodium carbonate solution was added. The mixture was extracted three times with dichloromethane. The dichloromethane was evaporated and the residue was purified by silica gel column chromatography, eluting with 0-40% ethyl acetate/hexane to give acetic acid 2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-yl ester (125 mg, 50%). 1H NMR (CDCl3) δ 2.38 (s, 3H), 2.46 (s, 3H), 7.56 (d, 1H, J=8.8 Hz), 7.77 (d, 1H, J=8.6 Hz), 8.10 (s, 1H), 9.16 (s, 1H).

Provenance & Evidence