4-fluoro-5-iodo-2-methoxybenzonitrile

反応条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 4-fluoro-5-iodo-2-methoxybenzonitrile (2.5 g, 9.0 mmol), Pd(Ph3P)4 (1.0 g, 0.90 mmol) and lithium chloride (0.96 g, 23 mmol) under nitrogen was added anhydrous toluene (50 mL) and the mixture was flushed (3×) with nitrogen. Allyltributyltin (4.15 mL, 14 mmol) was added and the mixture was flushed again with nitrogen. The reaction was heated under nitrogen at 115° C. for 2.5 hours and then let cool to room temperature. TLC (10% ethyl acetate/Hexanes) showed several spots with a strongly charring product spot right above the starting material. The reaction was diluted with hexanes and filtered to remove insoluble material. The mother liquor was concentrated and the residue was purified on a Biotage 65+M column with a gradient elution from 0 to 40% ethyl acetate in hexanes to afford the title product which had some residual tributylstanane by-product contaminant by NMR. 1H-NMR (500 MHz, CDCl3) δ ppm 3.327 (d, J=6.5 Hz, 2H), 3.902 (s, 3H), 5.102 (2 d, J=10.0 and 17 Hz, 2H), 5.868 (m, 1H), 6.668 (d, J=11.1 Hz, 1H), 7.390 (d, J=8.0 Hz, 1H). the mixture was flushed (3×) with nitrogen the mixture was flushed again with nitrogen let cool to room temperature The reaction was diluted with hexanes filtered to remove insoluble material The mother liquor was concentrated the residue was purified on a Biotage 65+M column with a gradient elution from 0 to 40% ethyl acetate in hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 4-fluoro-2-methoxybenzonitrile (3.00 g, 20 mmol) and N-iodosuccinimide (NIS) (4.7 g, 21 mmol) under nitrogen was added TFA (35 mL) and the reaction was stirred at room temperature for 20 hours. The volatiles were removed in vacuo and the residue was taken up in 1:1 ethyl acetate:ether and was washed with aqueous sodium bicarbonate and then brine containing enough sodium sulfite to remove the iodine color. The aqueous layers were back extracted with more 1:1 ethyl acetate:ether and the combined organic layers were dried over sodium sulfate and evaporated. The residue was treated with ether/hexanes to afford clean iodo title product as a white solid. 1H-NMR (500 MHz, CDCl3) δ ppm 3.930 (s, 3H), 6.730 (d, J=9.4 Hz, 1H), 7.900 (d, J=6.8 Hz, 1H). The volatiles were removed in vacuo ether and was washed with aqueous sodium bicarbonate brine containing enough sodium sulfite to remove the iodine color The aqueous layers were back extracted with more 1:1 ethyl acetate ether and the combined organic layers were dried over sodium sulfate evaporated The residue was treated with ether/hexanes