4-Fluoroiodobenzene → Methyl 1-(4-fluorophenyl)-1h-indole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a 3-L 4-neck flask equipped with mechanical stirrer, N2 inlet and thermocouple was added compound 1a (124 g, 0.71 mol), toluene (0.99 L), 4-fluoro-iodobenzene (cpd 3e, 314.27 g, 1.42 mol), racemic trans-N,N′-dimethylcyclohexane-1,2-diamine (cpd 3f, 30.2 g, 0.21 mol), copper iodide (13.48 g, 0.078 mol) and tribasic-N-hydrate potassium phosphate (330.54 g, 1.56 mol). The mixture was heated to 85° C. for 12 h. A second charge of 4-fluoro-iodobenzene (47.14 g, 0.21 mol) was added and the mixture was heated to 85° C. for 4 h. The reaction mixture was filtered through a diatomaceous earth pad and was washed with CH2Cl2 (2 L). The solvent was evaporated and the residue was purified by column chromatography (2.5 Kg Biotage SiO2 column, 15 column volumes, 10% EtOAc/Heptane) to give 110 g (58%) of compound 1c. 1H NMR (Chloroform-d) δ: 8.45 (d, J=1.5 Hz, 1H), 7.92 (dd, J=8.8, 1.5 Hz, 1H), 7.41-7.50 (m, 3H), 7.34 (d, J=3.2 Hz, 1H), 7.17-7.29 (m, 1H), 6.77 (d, J=3.4 Hz, 1H), 3.94 (s, 3H).

Provenance & Evidence