4-Fluoroiodobenzene → Ethyl 5-(4-fluorobenzyl)-3-[(4-fluorophenyl)amino]pyridine-2-carboxylate

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Reaction Steps

To a dry 100 mL flask under a nitrogen atmosphere was added ethyl 3-amino-5-(4-fluorobenzyl)pyridine-2-carboxylate (200 mg, 0.73 mmol) described in example 1, Cs2CO3 (333 mg, 1.02 mmol), Pd2dba3 (20.1 mg, 0.022 mmol), and Xantphos (38.2 mg, 0.066 mmol). Dioxane (15 mL) and 1-fluoro-4-iodobenzene (0.25 mL, 2.19 mmol) were added and the resulting solution was refluxed for 3 hrs or until judged complete by TLC (7:3 hexanes:ethyl acetate). The mixture was allowed to cool to ambient temperature, filtered through Celite eluting with dichloromethane and concentrated under reduced pressure. Purification by silica gel chromatography (0-45% ethyl acetate/hexanes gradient elution) afforded ethyl 5-(4-fluorobenzyl)-3-[(4-fluorophenyl)amino]pyridine-2-carboxylate (193 mg, 72% yield) as a yellow solid. 1H NMR (CDCl3) δ 9.35 (s, 1 H), 7.95 (s, 1 H), 7.14 (, s, 1 H), 7.10-6.99 (m, 6 H), 6.96-6.93 (m, 2 H), 4.46 (q, J=7.2 Hz, 2 H), 3.83 (s, 2 H), 1.44 (t, J=7.2 Hz, 3 H); MS m/z 369 (M+1).

Provenance & Evidence