Cesium carbonate → 2-Bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]-indolizin-2(1H)-yl)benzyl acetate

Participants

Reaction Conditions

Reaction Steps

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (60 mL), 2,6-dibromo-4-fluorobenzyl acetate (1.9 g, 6.0 mmol), 120d (400 mg, 2.0 mmol), and cesium carbonate (1.3 g, 4.0 mmol). After bubbling nitrogen through the resulting mixture for 30 minutes, Xantphos (120 mg, 0.2 mmol) and tris(dibenzylideneacetone)dipalladium(0) (180 mg, 0.2 mmol) were added, and the reaction mixture was heated at 100° C. for 12 h. After this time the reaction was cooled to room temperature, partitioned between ethyl acetate (40 mL) and water (40 mL), and filtered. The aqueous layer was separated and extracted with ethyl acetate (3×70 mL). The combined organic layer was washed with brine (30 mL) and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flush column eluting with 2:1 petroleum ether/ethyl acetate to afford 120e (421 mg, 46%) as yellow solid. MS: [M+H]+ 435. 1H NMR (500 MHz, MeOD) δ 7.52-7.50 (m, 1H), 7.23-7.20 (m, 1H), 6.14 (s, 1H), 5.20-5.10 (m, 2H), 4.09-4.06 (m, 1H), 3.95-3.92 (m, 1H), 3.88-3.85 (m, 1H), 3.78-3.75 (m, 1H), 3.07-2.97 (m, 2H), 2.81-2.77 (m, 2H), 2.03-2.00 (m, 5H), 1.87-1.84 (m, 2H).

Provenance & Evidence