Cesium carbonate → Ethyl (2-fluoro-4-((4-fluorobenzyl)amino)-6-nitrophenyl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of compound 2 (0.300 g, 0.790 mmol, 1.00 equiv) in 1,4-dioxane (10 mL) were added 4-fluorobenzylamine (0.200 g, 1.58 mmol, 2.00 equiv), Cs2CO3 (0.500 g, 1.50 mmol, 2.00 equiv) followed by Pd2 (dba)3 (0.072 g, 0.079 mmol, 10 mol %) and Xantphos (0.045 g, 0.079 mmol, 10 mol %) at RT. The reaction mixture was heated at 90° C. and stirred at the same temperature for 8 h. After consumption of the starting material (by TLC), the reaction mixture was concentrated under vacuum. The obtained residue was diluted with water (50 mL) and extracted with EtOAc (2×50 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude material was purified by silica gel column chromatography (EtOAc/Hexane 2:23) to afford compound 3 (0.140 g, 50.3%) as yellow solid. TLC: 40% EtOAc/Hexane (Rf: 0.25); 1H NMR (500 MHz, CDCl3): δ 7.31-7.28 (m, 2H), 7.06 (t, J=8.5 Hz, 1H), 7.00 (s, 2H), 6.91 (br s, 1H), 6.60 (d, J=9.5 Hz, 1H), 4.46 (br s, 1H), 4.31 (d, J=4.4 Hz, 2H), 4.20 (q, J=7.0 Hz, 2H), 1.28 (t, J=7.0 Hz, 3H); LC-MS: m/z=350 (M+-1) at RT 3.69 (97.8% purity).

Provenance & Evidence