4-Fluoroaniline → ethyl 5-ethoxy-2-(4-fluorophenyl)-2H-1,2,3-triazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of 4-fluoroaniline (11.1 g, 100 mmol) in water (50 mL) and concentrated hydrochloric acid (19 mL) was cooled to −15° C. To this mixture was added a previously cooled (0° C.) solution of sodium nitrite (7.6 g, 110 mmol) in water (25 mL) over 5 min. Ice was added directly to the reaction to maintain the temperature below 5° C. After the addition was complete, the reaction was stirred at 0° C. for 15 min. Sodium acetate (41.0 g, 500 mmol) was added followed by ethyl 3-ethoxy-3-iminopropionate (15.9 g, 100 mmol). A yellow precipitate formed immediately. The suspension was stirred at 23° C. for 30 min., and then the solid was filtered and washed with water (40 mL). The still wet hydrazone was dissolved in pyridine (150 mL). A solution of copper (II) sulfate (49.7 g, 199 mmol) in water (150 mL) was added at once. The dark mixture was heated to 90° C. for 4 h. The majority of the pyridine (˜100 mL) was removed under vacuum. The residue was diluted with ethyl acetate (200 mL), water (100 mL) and 2 M sulfuric acid (80 mL). The resulting emulsion was filtered through Celite® diatomaceaous earth filter aid. The organic layer was washed with 2 M sulfuric acid (2×100 mL), dried (MgSO4) and concentrated under reduced pressure. The resulting crude mixture was recrystallized from ethanol (80 mL) to obtain the title compound (15.1 g) as a pale red solid.

Provenance & Evidence