Cesium carbonate → 2-bromo-4-fluoro-6-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)benzyl acetate

Participants

Reaction Conditions

Reaction Steps

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 115k (3.8 g, 20 mmol), 2,6-dibromo-4-fluorobenzyl acetate 101c (20.0 g, 61 mmol), XantPhos (1.16 g, 2.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.83 g, 2.0 mmol), Cs2CO3 (16.3 g, 50 mmol), and 1,4-dioxane (120 mL). The system was evacuated and then refilled with N2. A reflux condenser was attached to the flask and the reaction mixture was heated at 100° C. for 16 h. The mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 5:1 petroleum ether/ethyl acetate to afford 115l as a white solid (5.2 g, 60%). MS: [M+H]+ 435. 1H NMR (500 MHz, DMSO-d6) δ 7.71-7.69 (m, 1H), 7.49-7.47 (m, 1H), 6.52 (s, 1H), 5.01 (m, 2H), 4.18 (m, 2H), 4.02 (m, 1H), 3.73 (m, 1H), 2.60 (m, 2H), 2.45 (m, 2H), 1.98 (s, 3H), 1.77 (m, 2H), 1.68 (m, 2H).

Provenance & Evidence