Citric Acid → 3-Bromo-1-(4-fluorophenyl)-1h-1,2,4-triazole

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-bromo-1,2,4-1H-triazole (prepared as described in Chemische Berichte 1967, 100, 2250) (1.0 g, 6.76 mmol), tri(4-fluorophenyl)bismuth diacetate (prepared by the method described in Synthetic Communications 1996, 4569) (4.53 g, 7.4 mmol), copper (II) acetate (0.25 g, 20 mol %) and N,N,N′,N′-tetramethylguanidine (1.7 mL, 13.5 mmol) in dry tetrahydrofuran (30 mL) was stirred at 50° C. under a balloon of air for 16 hr. The suspension was poured into water (100 mL) and 1M citric acid (30 mL) to give a suspension of pH 3-4. Ethyl acetate (100 mL) was added and the mixture was filtered through Celite®, washing the filter cake with ethyl acetate (100 mL). The two phases of the filtrate were separated and the organic layer was dried (Na2SO4) and concentrated. Flash column chromatography on silica gel, eluting with 25% then 40% ethyl acetate—isohexane, gave 1-(4-fluorophenyl)-3-bromo-1,2,4-1H-triazole as an off-white solid (0.74 g, 45%). δ (1H, 400 MHz, CDCl3) 7.18-7.24 (2H, m), 7.60-7.65 (2H, m), 8.37 (1H, s). MS (ES+) 242, 244 ([MH]+). Step 2: [6S,9R,11R] 2′,3′,4′,5,5′,6,7,8,9,10-Decahydro-2-(1-(4-fluorophenyl)-1,2,4-triazol-3-yl)-5′-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3′-[1,2,5]thiadiazole] 1′,1′-dioxide

Provenance & Evidence