Triethylamine → HCID 58368582, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 5-chloro-2-hydroxy-3-nitro-4-[(trimethylsilyl)ethynyl]benzoate (380 g, 1.2 mol) in toluene (3.7 L) at −12° C. was treated with triethylamine (320 mL, 2.3 mol), followed by trifluoromethanesulfonic anhydride (270 mL, 1.6 mol) dropwise over a 15 minute period (temperature was −3° C. at the end of the addition). The dry ice/isopropanol bath was removed. The reaction mixture was kept at −15 to 20° C. for 3 hours. The reaction mixture was treated with water (3.2 L) and stirred for 20 minutes. The organic layer was separated and rinsed with water (2×1.6 L). The organic layer containing the triflate intermediate was used immediately without further purification. The triflate solution was treated with water (1.9 L), sodium bicarbonate (390 g, 4.6 mol), (3-fluorophenyl)boronic acid (210 g, 1.5 mol) and the mixture was degassed with nitrogen for approximately 10 minutes. The reaction mixture was treated with tetrakis(triphenylphosphine)palladium(0) (27 g, 23 mmol), degassed with nitrogen for an additional 10 minutes, and heated to 80° C. for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (2 L) and water (2 L), and stirred. The organic layer was separated and washed with water (2×2 L) and brine. Celite (150 g) was added to the organic layer and the mixture was stirred for 30 minutes. The organic layer was filtered through a pad of celite, rinsed with ethyl acetate (1 L), and concentrated to give a dark green solid. The solid was diluted with isopropanol (3 L) and heated to 70° C. which gave a dark green solution. The solution was stirred at room temperature for 2 hours and at 0° C. for 30 minutes. The solid was collected by filtration, rinsed with isopropanol (800 mL), and dried to give the desired product (330 g, 71%) as a green solid. HPLC 98.9% pure @ 220 nm. LCMS for C19H18ClFNO4Si (M+H)+: m/z=406.1; Found: 405.9; 1H NMR (300 MHz, DMSO-d6): δ 8.27 (s, 1 H), 7.52-7.41 (m, 1 H), 7.35-7.23 (m, 1 H), 7.19-7.11 (m, 1 H), 7.09-7.02 (m, 1 H), 3.58 (s, 3 H), 0.22 (s, 9 H).

Provenance & Evidence